)| PMID |
14766238 ( ) |
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| Title | Heme oxygenase-1 prevents superoxide anion-associated endothelial cell sloughing in diabetic rats. |
| Abstract | Heme oxygenase-1 (HO-1) represents a key defense mechanism against oxidative injury. Hyperglycemia has been linked to increased oxidative stress, leading to endothelial dysfunction, delayed cell replication, and enhanced apoptosis. The effect of streptozotocin (STZ)-induced diabetes on HO activity, HO-1 promoter activity, superoxide anion (O*-2, and the number of circulating endothelial cells was measured. The expression of HO-1/HO-2 protein was unchanged, but HO activity was decreased in aortas of diabetic rats compared with control (p < 0.05). High glucose decreased HO-1 promoter activity (p < 0.05). Hyperglycemia increased O*-2 and this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation (p < 0.05). Circulating endothelial cells were significantly higher in diabetic rats and were decreased or increased with administration of the HO-1 inducer (CoPP) or inhibitor (SnMP), respectively (p<0.05). In conclusion, HO-1 upregulation in diabetic rats brings about an increase in serum bilirubin, a reduction in O*-2 production, and a decrease in endothelial cell sloughing. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | 137 | HO-1 | heme oxygenase 1 | ho 1 | |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | 19 | ho 2 | HO-2 | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 4 | angiotensin ii | ang ii | |
| 19986 | CYCS | cytochrome c, somatic | 3 | cytochrome c | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 3 | nadph oxidase | |
| 3229 | EGF | epidermal growth factor (beta-urogastrone) | 2 | EGF | epidermal growth factor | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91 phox | |
| 399 | ALB | albumin | 1 | serum albumin | |
| 4827 | HBB | hemoglobin, beta | 1 | hemoglobin | |
| 9393 | PRKCA | protein kinase C, alpha | 1 | protein kinase c | |
| 8823 | PECAM1 | platelet/endothelial cell adhesion molecule (CD31 antigen) | 1 | CD31 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | p22 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 1 | superoxide dismutase | |
| 12726 | VWF | von Willebrand factor | 1 | vWF | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Heme oxygenase-1 (HO-1) HO-1 represents a key defense mechanism against oxidative injury |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | effect of streptozotocin (STZ)-induced STZ -induced diabetes on HO activity HO-1 promoter activity superoxide anion (O O _amp_#x221a _amp_#x2212 2 and |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | of circulating endothelial cells was measured The expression of HO-1/HO-2 HO-1 HO-2 protein was unchanged but HO activity was decreased in |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | circulating endothelial cells was measured The expression of HO-1/HO-2 HO-1 HO-2 protein was unchanged but HO activity was decreased in aortas |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | High glucose decreased HO-1 promoter activity (p_amp_#x3c;0.05) p_amp_#x3c 0.05 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | O _amp_#x221a _amp_#x2212 2 and this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation (p_amp_#x3c;0.05) p_amp_#x3c 0.05 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation (p_amp_#x3c;0.05) p_amp_#x3c 0.05 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | rats and were decreased or increased with administration of the HO-1 inducer (CoPP) CoPP or inhibitor (SnMP), SnMP respectively (p_amp_#x3c;0.05) p_amp_#x3c |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | In conclusion HO-1 upregulation in diabetic rats brings about an increase in serum |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Heme oxygenase-1 (HO-1) HO-1 is considered to be an anti-oxidant 13 that is induced |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | The anti-oxidant capacity of HO-1 stems from its ability to degrade heme 22 and to |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | HO-1 expression is also known to enhance ferritin synthesis which lowers |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Another product of HO-1 is carbon monoxide (CO), CO which has been shown to |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Thus HO-1 expression could have a major influence on the biological effect |
| 4827 | HBB | hemoglobin, beta | hemoglobin | 1.0 | sickle cell anemia elevation of cellular heme levels from denatured hemoglobin in these patients plays an important role in the vaso-occlusions |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | hyperglycemia on overall HO activity and expression of the specific HO-1 and HO-2 proteins in vivo and to examine the role |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | hyperglycemia on overall HO activity and expression of the specific HO-1 and HO-2 proteins in vivo and to examine the role |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | overall HO activity and expression of the specific HO-1 and HO-2 proteins in vivo and to examine the role of overexpression |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | and to examine the role of overexpression or suppression of HO-1 in endothelial cell shedding O _amp_#x221a _amp_#x2212 2 production and |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Rats were injected with a potent inducer of HO-1 cobalt protoporphyrin (CoPP), CoPP or inhibitor of HO activity stannous |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | (SnMP), SnMP which were used to assess the relationship of HO-1 gene expression to these parameters |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Upregulation of HO-1 by CoPP attenuated the hyperglycemia-mediated increase in circulating endothelial cells |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | hyperglycemia-mediated increase in circulating endothelial cells whereas underexpression of rat HO-1 magnified these effects |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | in O _amp_#x221a _amp_#x2212 2 substantiating a significant role for HO-1 as part of the cellular defense system against oxidant damage |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Upregulation of HO-1 may provide a novel protective mechanism against vascular endothelial injury |
| 3229 | EGF | epidermal growth factor (beta-urogastrone) | EGF | 1.2 | 10% FBS 10 ng/ml ng ml epidermal growth factor (EGF; EGF Sigma St Louis MO and 1 _amp_#x3bc;g/ml _amp_#x3bc g ml |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | by releasing a 1519-bp (+19 19 to _amp_#x2212 1500 human HO-1 transcription regulatory sequence (HOP) HOP from the plasmid pGEM-HOP 38 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Western blotting for HO-1 and HO-2 |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | Western blotting for HO-1 and HO-2 |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | Western blotting for HO-1 and HO-2 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Protein levels were visualized by immunoblotting with antibodies against human HO-1 rat HO-1 or HO-2 (Stressgen Stressgen Biotechnologies Victoria BC |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | were visualized by immunoblotting with antibodies against human HO-1 rat HO-1 or HO-2 (Stressgen Stressgen Biotechnologies Victoria BC |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | by immunoblotting with antibodies against human HO-1 rat HO-1 or HO-2 (Stressgen Stressgen Biotechnologies Victoria BC |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Results HO-1 and HO-2 expression in STZ-induced diabetic rats |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | Results HO-1 and HO-2 expression in STZ-induced diabetic rats |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | Results HO-1 and HO-2 expression in STZ-induced diabetic rats |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | As shown in Fig 1A HO-1/HO-2 HO-1 HO-2 protein expression was not significantly changed in aorta of |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | As shown in Fig 1A HO-1/HO-2 HO-1 HO-2 protein expression was not significantly changed in aorta of diabetic |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | However the administration of CoPP (an an HO-1 inducer 0.5 mg/kg, mg kg ip weekly or SnMP (an |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | 0.5 mg/kg, mg kg ip weekly or SnMP (an an HO-1 inhibitor 10 _amp_#x3bc;mol/100 _amp_#x3bc mol 100 g iv weekly increased |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | inhibitor 10 _amp_#x3bc;mol/100 _amp_#x3bc mol 100 g iv weekly increased HO-1 protein expression |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Transcriptional regulation of HO-1 gene in response to different time/concentrations time concentrations of glucose |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Since glucose has been shown to inhibit HO-1 protein and HO activity in human endothelial cells in culture |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | 44 we examined the mechanism by which glucose may affect HO-1 activity |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | We studied the ability of three different lengths of human HO-1 transcription regulatory sequences (promoters) promoters to drive luciferase reporter gene |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Three different lengths of HO-1 promoters were used to control firefly luciferase reporter gene transcription |
| 12726 | VWF | von Willebrand factor | vWF | 0.3 | in STZ-induced diabetic rats these cells reproducibly stained positive for vWF CD31 and UEA-1 which was regarded as sufficient proof of |
| 8823 | PECAM1 | platelet/endothelial cell adhesion molecule (CD31 antigen) | CD31 | 1.6 | STZ-induced diabetic rats these cells reproducibly stained positive for vWF CD31 and UEA-1 which was regarded as sufficient proof of their |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | The administration of CoPP an HO-1 inducer significantly decreased the number of circulating endothelial cells (28 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | 0.01 compared to STZ rats while treatment with SnMP an HO-1 inhibitor increased the number of circulating endothelial cells (56 56 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | These data suggest that the induction of HO-1 expression contributes to the decreased production of circulating endothelial cells |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | The decrease in HO-1 activity and low levels in serum bilirubin in diabetic rats |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | In contrast the CoPP-mediated increase in HO-1 and HO activity decreased O 2 _amp_#x2212 production below control |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Further inhibition of HO activity by SnMP (inhibits inhibits both HO-1 and HO-2 activity decreased plasma bilirubin and increased O 2 |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | Further inhibition of HO activity by SnMP (inhibits inhibits both HO-1 and HO-2 activity decreased plasma bilirubin and increased O 2 |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | HO-2 | 3.4 | of HO activity by SnMP (inhibits inhibits both HO-1 and HO-2 activity decreased plasma bilirubin and increased O 2 _amp_#x2212 production |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | we made several novel findings to support the notion that HO-1 expression plays a role in amelioration of diabetic vascular complications |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | an inhibition of HO activity without a significant change in HO-1 protein expression in the aorta of STZ-induced diabetic rats ( |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | the conventional known effect of oxidants which is to increase HO-1 gene expression as an adaptive response to ROS 13 and |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | are in agreement with the finding that glucose deprivation increases HO-1 protein which can be by the addition of glucose 48 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | the synthesis and binding of gp91 (phox) phox to the p22 subunit of NADPH oxidase necessary for its activity 52 53 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Therefore upregulation of HO-1 gene expression may decrease the binding of the gp91 subunit |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | In contrast a decrease in HO-1 may magnify the heme-mediated activation of NADPH oxidase and O |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | To further explore the mechanism of HO-1 gene regulation in response to high glucose we studied the |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | glucose we studied the ability of three different lengths of HO-1 promoters in driving luciferase reporter gene expression in transfected endothelial |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | The data revealed that high glucose decreased HO-1 expression as seen in decrease in the levels of the |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | activity but had no effect on 2.7 or 1.5 kb HO-1 promoter (data data not shown |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Further the administration of an HO-1 inducer (CoPP) CoPP or inhibitor (SnMP) SnMP decreased or increased |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | In addition to glycemic control the upregulation of HO-1 expression represents a potential alternative therapeutic strategy for delaying and |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | In view of the fact that induction of HO-1 by CoPP results in the generation of CO and CO |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | 31 and 32 and the fact that second product of HO-1 activity bilirubin is a potent anti-oxidant which has been shown |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | We suggest that HO-1 upregulation and increase in serum bilirubin resulting in a decrease |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | The regulation of HO-1 gene expression however is much more complicated in vivo and |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | is much more complicated in vivo and the level of HO-1 gene expression can be attributed to the balance between stimulatory |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Indeed it has been reported that HO-1 expression can be increased decreased or unchanged 6 44 57 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Other investigators have shown that intramuscular and ocular HO-1 mRNA is reduced in patients with Type 2 diabetes with |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Others have shown that with a decrease in HO-1 expression or HO activity in mice or in a human |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | HO activity in mice or in a human lacking functional HO-1 the levels of oxidants and oxidative stress-mediated cell injury were |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | HO by the addition of SnMP or in cells underexpressing HO-1 resulted in increased cellular heme and decreased generation of the |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Mazza et al 56 have shown that a decrease in HO-1 proteins increased DNA degradation |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Thus HO-1 expression could have a major influence on the biological effect |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Ang II alone resulted in an increase in HO-1 as a protective mechanism against ROS in vitro and in |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Upregulation of HO by an HO-1 inducer and increase in serum bilirubin may provide a novel |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | (A) A Western blot analysis of aorta HO-1 protein expression in STZ-induced diabetic rats |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | HO-1 inducer (CoPP) CoPP or inhibitor (SnMP) SnMP was administered as |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | Four weeks after injection with STZ aorta HO-1 expression was examined * p _amp_#x3c 0.05 vs control # |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | High glucose decreased 11.6Kb HO-1 promoter activity as demonstrated by luciferase activity for 24 h |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | HO-1 | 8.9 | The administration of HO-1 inducer (CoPP) CoPP or inhibitor (SnMP) SnMP decreased or increased |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | heme oxygenase 1 ho 1 represents a key defense mechanism against oxidative injury. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | heme oxygenase 1 | 1.0 | heme oxygenase 1 ho 1 represents a key defense mechanism against oxidative injury. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the effect of streptozotocin stz induced diabetes on ho activity ho 1 promoter activity superoxide anion o _amp_#x221a;_amp_#x2212; 2 and the number of circulating endothelial cells was measured the expression of ho 1/ho 2 protein was unchanged but ho activity was decr |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | promoter activity superoxide anion o _amp_#x221a;_amp_#x2212; 2 and the number of circulating endothelial cells was measured the expression of ho 1/ho 2 protein was unchanged but ho activity was decreased in aortas of diabetic rats compared with control p_amp_#x3c;0.05 . |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | ptozotocin stz induced diabetes on ho activity ho 1 promoter activity superoxide anion o _amp_#x221a;_amp_#x2212; 2 and the number of circulating endothelial cells was measured the expression of ho 1/ho 2 protein was unchanged but ho activity was decreased in aortas of diabetic rats compared with control p_amp_#x3c;0.05 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | high glucose decreased ho 1 promoter activity p_amp_#x3c;0.05 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | hyperglycemia increased o _amp_#x221a;_amp_#x2212; 2 and this increase was augmented with ho 1 inhibition and diminished with ho 1 upregulation p_amp_#x3c;0.05 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | circulating endothelial cells were significantly higher in diabetic rats and were decreased or increased with administration of the ho 1 inducer copp or inhibitor snmp respectively p_amp_#x3c;0.05 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | in conclusion ho 1 upregulation in diabetic rats brings about an increase in serum bilirubin a reduction in o _amp_#x221a;_amp_#x2212; 2 production and a decrease in endothelial cell sloughing. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | hyperglycemia is known to increase the levels of the reactive oxygen species ros and superoxide anion via mechanisms that include an increase in protein kinase c [ 4 ] and lipoxygenase [ 5 ] and an increase in cellular heme and free radicals [ 6 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | heme oxygenase 1 ho 1 is considered to be an anti oxidant [ 13 ] that is induced by oxidants generating molecules including angiotensin ii [ 14 15 and 16 ] heme [ 13 ] and pro inflammatory cytokines [ 17 18 19 and 20 ] and tgf _amp_#x3b2;1 [ 21 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | heme oxygenase 1 ho 1 is considered to be an anti oxidant [ 13 ] that is induced by oxidants generating molecules including angiotensin ii [ 14 15 and 16 ] heme [ 13 ] and pro inflammatory cytokines [ 17 18 19 and 20 ] an |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | heme oxygenase 1 | 1.0 | heme oxygenase 1 ho 1 is considered to be an anti oxidant [ 13 ] that is induced by oxidants generating molecules including angiotensin ii [ 14 15 and 16 ] heme [ 13 ] and pro inflammatory cytokines [ 17 18 19 and 20 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the anti oxidant capacity of ho 1 stems from its ability to degrade heme [ 22 ] and to generate biliverdin/bilirubin which has potent anti oxidant effects [ 23 and 24 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | ho 1 expression is also known to enhance ferritin synthesis which lowers intracellular iron and free radicals [ 25 26 and 27 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | another product of ho 1 is carbon monoxide co which has been shown to provide cytoprotective actions [ 28 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | thus ho 1 expression could have a major influence on the biological effect of oxidant stress. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the objectives of this study were to determine the effects of hyperglycemia on overall ho activity and expression of the specific ho 1 and ho 2 proteins in vivo and to examine the role of overexpression or suppression of ho 1 in endothelial cell shedding o _amp_#x221a;_amp_#x2212; 2 production and heme levels in the experimental dia |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | and ho 2 proteins in vivo and to examine the role of overexpression or suppression of ho 1 in endothelial cell shedding o _amp_#x221a;_amp_#x2212; 2 production and heme levels in the experimental diabetic state. |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | the objectives of this study were to determine the effects of hyperglycemia on overall ho activity and expression of the specific ho 1 and ho 2 proteins in vivo and to examine the role of overexpression or suppression of ho 1 in endothelial cell shedding o _amp_#x221a;_amp_#x2212; 2 production and heme levels in the experimental diabetic sta |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | rats were injected with a potent inducer of ho 1 cobalt protoporphyrin copp or inhibitor of ho activity stannous mesoporphyrin snmp which were used to assess the relationship of ho 1 gene expression to these parameters. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | upregulation of ho 1 by copp attenuated the hyperglycemia mediated increase in circulating endothelial cells whereas underexpression of rat ho 1 magnified these effects. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | further copp attenuated the diabetes mediated increase in o _amp_#x221a;_amp_#x2212; 2 substantiating a significant role for ho 1 as part of the cellular defense system against oxidant damage in the vascular endothelium. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | upregulation of ho 1 may provide a novel protective mechanism against vascular endothelial injury. |
| 3229 | EGF | epidermal growth factor (beta-urogastrone) | epidermal growth factor | 1.0 | human dermal microvessel endothelial cells were grown in mcdb131 medium gibco/brl grand island ny supplemented with 10% fbs 10 ng/ml epidermal growth factor egf; sigma st louis mo and 1 _amp_#x3bc;g/ml hydrocortisone sigma_amp_#x2013;aldrich st louis mo . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the plasmid hop1.5k luc was constructed by releasing a 1519 bp +19 to _amp_#x2212;1500 human ho 1 transcription regulatory sequence hop from the plasmid pgem hop [ 38 ] and inserting it at the xho i and sac i sites of the luciferase reporter gene plasmid pgl3 basic promega madison wi . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | western blotting for ho 1 and ho 2 . |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | western blotting for ho 1 and ho 2 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | protein levels were visualized by immunoblotting with antibodies against human ho 1 rat ho 1 or ho 2 stressgen biotechnologies victoria bc . |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | protein levels were visualized by immunoblotting with antibodies against human ho 1 rat ho 1 or ho 2 stressgen biotechnologies victoria bc . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | after washing with tbst the membranes were incubated with a 1:2000 dilution of anti ho 1 or anti ho 2 antibodies for 1 h at room temperature with constant shaking. |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | after washing with tbst the membranes were incubated with a 1:2000 dilution of anti ho 1 or anti ho 2 antibodies for 1 h at room temperature with constant shaking. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | tissue homogenates were incubated with 0.5 ml reaction mixture consisting of krebs ringer phosphate buffer containing 80 _amp_#x3bc;m cytochrome c and 2 mm nan 3 . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | samples were also incubated in the presence and absence of 300 u superoxide dismutase. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | after 1 h of incubation at 37 _amp_#xb0;c the supernatants immediately were collected and used to assay the amount of reduced cytochrome c by the difference in absorbance at 550 468 nm using the extinction coefficient of 21.1 mm _amp_#x2212;1 cm _amp_#x2212;1 for reduced ferricytochrome c as previously described 1 . |
| 399 | ALB | albumin | serum albumin | 1.0 | bated overnight at 4 _amp_#xb0;c under head over head agitation with 1 ml of a solution of reca 1 medac diagnostica hamburg germany diluted 1:10 in buffer phosphate buffered solution plus 0.1% bovine serum albumin . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | results ho 1 and ho 2 expression in stz induced diabetic rats |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | results ho 1 and ho 2 expression in stz induced diabetic rats |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | as shown in fig. 1a ho 1/ho 2 protein expression was not significantly changed in aorta of diabetic rats relative to control rats. |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | as shown in fig. 1a ho 1/ho 2 protein expression was not significantly changed in aorta of diabetic rats relative to control rats. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | however the administration of copp an ho 1 inducer 0.5 mg/kg ip weekly or snmp an ho 1 inhibitor 10 _amp_#x3bc;mol/100 g iv weekly increased ho 1 protein expression. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | transcriptional regulation of ho 1 gene in response to different time/concentrations of glucose treatment |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | since glucose has been shown to inhibit ho 1 protein and ho activity in human endothelial cells in culture [ 6 ] and in diabetic rats [ 42 43 and 44 ] we examined the mechanism by which glucose may affect ho 1 activity. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | protein and ho activity in human endothelial cells in culture [ 6 ] and in diabetic rats [ 42 43 and 44 ] we examined the mechanism by which glucose may affect ho 1 activity. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | we studied the ability of three different lengths of human ho 1 transcription regulatory sequences promoters to drive luciferase reporter gene expression in transfected human microvessel endothelial cells under high glucose conditions. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | three different lengths of ho 1 promoters were used to control firefly luciferase reporter gene transcription. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the administration of copp an ho 1 inducer significantly decreased the number of circulating endothelial cells 28 _amp_#xb1; 5 cells/ml p _amp_#x3c;0.01 compared to stz rats while treatment with snmp an ho 1 inhibitor increased the nu |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | inducer significantly decreased the number of circulating endothelial cells 28 _amp_#xb1; 5 cells/ml p _amp_#x3c;0.01 compared to stz rats while treatment with snmp an ho 1 inhibitor increased the number of circulating endothelial cells 56 _amp_#xb1; 12 p _amp_#x3c;0.01 relative to stz rats . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | these data suggest that the induction of ho 1 expression contributes to the decreased production of circulating endothelial cells in stz induced diabetic rats and may provide a novel means for protection against endothelial apoptosis and damage. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | as seen in table 1 the increase in ho 1 derived bilirubin as a result of copp administration was closely associated with a decrease in o 2 _amp_#x2212; whereas the decrease in bilirubin in diabetic rats was associated with an increase in o |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | although the methods using lucigenin and detection by chemiluminescence were reproducible we compared this method to spectrophotometric using cytochrome c reduction. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the decrease in ho 1 activity and low levels in serum bilirubin in diabetic rats was consistent with the effect of hyperglycemia on the formation of o 2 _amp_#x2212; which increased from 1.59 _amp_#xb1; 0.14 _amp_#x3bc;m |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | in contrast the copp mediated increase in ho 1 and ho activity decreased o 2 _amp_#x2212; production below control levels 1.03 _amp_#xb1; 0.11 _amp_#x3bc;mol/mg. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | further inhibition of ho activity by snmp inhibits both ho 1 and ho 2 activity decreased plasma bilirubin and increased o 2 _amp_#x2212; production data not shown and that there is inverse relationship between bilirubin levels and o 2 _amp_#x2212; production. |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | further inhibition of ho activity by snmp inhibits both ho 1 and ho 2 activity decreased plasma bilirubin and increased o 2 _amp_#x2212; production data not shown and that there is inverse relationship between bilirubin levels and o 2 _amp_#x2212; production. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | in the present study we made several novel findings to support the notion that ho 1 expression plays a role in amelioration of diabetic vascular complications. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | first we observed that in early development hyperglycemia there was an inhibition of ho activity without a significant change in ho 1 protein expression in the aorta of stz induced diabetic rats p _amp_#x3c;0.05 relative to vehicle treated control rats. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | this contradicts the conventional known effect of oxidants which is to increase ho 1 gene expression as an adaptive response to ros [ 13 and 47 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | however the present data are in agreement with the finding that glucose deprivation increases ho 1 protein which can be by the addition of glucose [ 48 ]. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | heme levels are critical for the synthesis and binding of gp91 phox to the p22 subunit of nadph oxidase necessary for its activity [ 52 53 and 54 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | heme levels are critical for the synthesis and binding of gp91 phox to the p22 subunit of nadph oxidase necessary for its activity [ 52 53 and 54 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | therefore upregulation of ho 1 gene expression may decrease the binding of the gp91 subunit necessary for nadph oxidase activity and the generation of o _amp_#x2212; 2 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | therefore upregulation of ho 1 gene expression may decrease the binding of the gp91 subunit necessary for nadph oxidase activity and the generation of o _amp_#x2212; 2 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in contrast a decrease in ho 1 may magnify the heme mediated activation of nadph oxidase and o _amp_#x2212; 2 generation in diabetes. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | in contrast a decrease in ho 1 may magnify the heme mediated activation of nadph oxidase and o _amp_#x2212; 2 generation in diabetes. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | to further explore the mechanism of ho 1 gene regulation in response to high glucose we studied the ability of three different lengths of ho 1 promoters in driving luciferase reporter gene expression in transfected endothelial cells. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the data revealed that high glucose decreased ho 1 expression as seen in decrease in the levels of the promoter 11.6 kb activity but had no effect on 2.7 or 1.5 kb ho 1 promoter data not shown . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | further the administration of an ho 1 inducer copp or inhibitor snmp decreased or increased the production of circulating endothelial cells respectively. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | in addition to glycemic control the upregulation of ho 1 expression represents a potential alternative therapeutic strategy for delaying and slowing the progression of diabetic vascular complications [ 55 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | in view of the fact that induction of ho 1 by copp results in the generation of co and co has been shown to have anti apoptotic properties [ 31 and 32 ] and the fact that second product of ho 1 activity bilirubin is a potent anti oxidant which has been shown to attenuate oxidative mediated dna damage [ 56 ] and glucose mediated apoptosis [ 6 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | we suggest that ho 1 upregulation and increase in serum bilirubin resulting in a decrease in o _amp_#x2212; 2 may decrease circulating endothelial cells in diabetic blood. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the regulation of ho 1 gene expression however is much more complicated in vivo and the level of ho 1 gene expression can be attributed to the balance between stimulatory and inhibitory factors. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | indeed it has been reported that ho 1 expression can be increased decreased or unchanged [ 6 44 57 58 and 59 ] depending on individual experimental conditions i.e. tissue type level of blood glucose and severity of diabetes. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | other investigators have shown that intramuscular and ocular ho 1 mrna is reduced in patients with type 2 diabetes with a disturbed anti oxidant defense mechanism [ 59 and 60 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | others have shown that with a decrease in ho 1 expression or ho activity in mice or in a human lacking functional ho 1 the levels of oxidants and oxidative stress mediated cell injury were significantly increased providing strong support for the concept that this enzyme confers protection against oxidative stress [ 6 |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | indeed inhibition of ho by the addition of snmp or in cells underexpressing ho 1 resulted in increased cellular heme and decreased generation of the anti oxidant bilirubin and oxidative stress [ 38 and 40 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | mazza et al. [ 56 ] have shown that a decrease in ho 1 proteins increased dna degradation. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | thus ho 1 expression could have a major influence on the biological effect of oxidant stress. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in addition to glucose mediated increases in oxidative stress high glucose enhances the levels of angiotensin ii ang ii the latter also enhances ros [ 67 and 68 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | in addition to glucose mediated increases in oxidative stress high glucose enhances the levels of angiotensin ii ang ii the latter also enhances ros [ 67 and 68 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | ang ii alone resulted in an increase in ho 1 as a protective mechanism against ros in vitro and in vivo [ 14 15 and 16 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | ang ii alone resulted in an increase in ho 1 as a protective mechanism against ros in vitro and in vivo [ 14 15 and 16 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | upregulation of ho by an ho 1 inducer and increase in serum bilirubin may provide a novel means to ameliorate endothelial injury in diabetes. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | a western blot analysis of aorta ho 1 protein expression in stz induced diabetic rats. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | ho 1 inducer copp or inhibitor snmp was administered as described in materials and methods. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | four weeks after injection with stz aorta ho 1 expression was examined. * p _amp_#x3c;0.05 vs. control. # p _amp_#x3c;0.05 vs. stz + snmp. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | high glucose decreased 11.6kb ho 1 promoter activity as demonstrated by luciferase activity for 24 h n =6 * p _amp_#x3c;0.05 vs. corresponding low glucose treated cells. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | ho 1 | 1.0 | the administration of ho 1 inducer copp or inhibitor snmp decreased or increased cecs respectively n =6_amp_#x2013;8. * p _amp_#x3c;0.05 vs. control # p _amp_#x3c;0.05 vs. stz. |