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17346751 ( ) |
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| Title | Induction of reactive oxygen species from isolated rat glomeruli by protein kinase C activation and TNF-alpha stimulation, and effects of a phosphodiesterase inhibitor. |
| Abstract | Diabetic nephropathy is a major complication of diabetes leading to end-stage renal disease, which requires hemodialysis. Although the mechanism by which it progresses is largely unknown, the role of hyperglycemia-derived oxidative stress has recently been the focus of attention as the cause of diabetic complications. Constituent cells of the renal glomeruli have the capacity to release reactive oxygen species (ROS) upon stimulation of NADPH oxidase activated by protein kinase C (PKC). Hyperglycemia and insulin resistance in the diabetic state are often associated with activation of PKC and tumor necrosis factor (TNF)-alpha, respectively. The aim of this study is to clarify the signaling pathway leading to ROS production by PKC and TNF-alpha in rat glomeruli. Isolated rat glomeruli were stimulated with phorbol 12-myristate 13-acetate (PMA) and TNF-alpha, and the amount of ROS was measured using a chemiluminescence method. Stimulation with PMA (10 ng/ml) generated ROS with a peak value of 136+/-1.2 cpm/mg protein (mean+/-SEM). The PKC inhibitor H-7, the NADPH oxidase inhibitor diphenylene iodonium and the phosphatidylinositol-3 (PI-3) kinase inhibitor wortmannin inhibited PMA-induced ROS production by 100%, 100% and 80%, respectively. In addition, TNF-alpha stimulated ROS production (283+/-5.8/mg protein/20 min). The phosphodiesterase inhibitor cilostazol activates protein kinase A and is reported to improve albuminuria in diabetic rats. Cilostazol (100 microg/ml) inhibited PMA, and TNF-alpha-induced ROS production by 78+/-1.8, and 19+/-2.7%, respectively. The effects of cilostazol were not additive with wortmannin. Cilostazol arrests oxidative stress induced by PKC activation by inhibiting the PI-3 kinase-dependent pathway, and may thus prevent the development of diabetic nephropathy. Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa, Ishikawa, Japan. |
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 |
|---|---|---|---|---|
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 43 | tumor necrosis factor | TNF-A | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 32 | nadph oxidase | |
| 6081 | INS | insulin | 4 | insulin | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 3 | MAP | MAPK-pathways. | |
| 399 | ALB | albumin | 2 | albumin | serum albumin | |
| 9393 | PRKCA | protein kinase C, alpha | 2 | protein kinase c | |
| 7891 | NOX4 | NADPH oxidase 4 | 2 | NOX4 | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91 phox | |
| 9855 | RAP1A | RAP1A, member of RAS oncogene family | 1 | rap1a | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 1 | angiotensin converting enzyme | |
| 11765 | TGFA | transforming growth factor, alpha | 1 | transforming growth factor | |
| 9391 | PRKAR2A | protein kinase, cAMP-dependent, regulatory, type II, alpha | 1 | protein kinase a | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 1.2 | associated with activation of PKC and tumor necrosis factor (TNF)-_amp_#x3b1;, TNF -_amp_#x3b1 respectively |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | the signaling pathway leading to ROS production by PKC and TNF-_amp_#x3b1 in rat glomeruli |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | glomeruli were stimulated with phorbol 12-myristate 13-acetate (PMA) PMA and TNF-_amp_#x3b1 and the amount of ROS was measured using a chemiluminescence |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | In addition TNF-_amp_#x3b1 stimulated ROS production (283 283 _amp_#xb1 5.8/mg 5.8 mg protein/20_amp_#xa0;min) |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Cilostazol (100_amp_#xa0;_amp_#x3bc;g/ml) 100_amp_#xa0 _amp_#x3bc g ml inhibited PMA and TNF-_amp_#x3b1 -induced ROS production by 78 _amp_#xb1 1.8 and 19 _amp_#xb1 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Activated macrophages secrete tumor necrosis factor-_amp_#x3b1 (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 (Beutler Beutler et al. 1985 which is involved in the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | In inflamed tissue TNF-_amp_#x3b1 alone facilitates the production of ROS by neutrophils |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | redox environment may be involved as an onset factor for TNF-_amp_#x3b1 -induced cytotoxicity and as a study suggested the usefulness of |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | of antioxidants ( Toborek et al. 1995 it appears that TNF-_amp_#x3b1 is a cytokine that further exacerbates oxidative stress in diabetic |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | rat glomeruli to determine whether ROS production is induced by TNF-_amp_#x3b1 which is elevated by obesity and causes insulin resistance ( |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 stimulation |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | a preliminary study showed that increases in chemiluminescence due to TNF-_amp_#x3b1 stimulation did not have a clear peak total chemiluminescence over |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | a clear peak total chemiluminescence over a 20-min period after TNF-_amp_#x3b1 stimulation was determined |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | In other words after adding recombinant TNF-_amp_#x3b1 (final final concentration 10_amp_#xa0;ng/ml, 10_amp_#xa0 ng ml Pepro Tech Rocky |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | added and the level of ROS production following PMA or TNF-_amp_#x3b1 stimulation was measured as mentioned above |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 stimulation |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Fig 1 b shows the results of glomerular stimulation by TNF-_amp_#x3b1 (final final concentration 10_amp_#xa0;ng/ml) 10_amp_#xa0 ng ml |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | in chemiluminescence seen after PMA stimulation was not seen with TNF-_amp_#x3b1 stimulation and low chemiluminescence (below below 25_amp_#xa0 cpm continued for |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | As shown in Fig 3 total chemiluminescence with TNF-_amp_#x3b1 stimulation was 283 _amp_#xb1 6.78 count/mg count mg protein/20_amp_#xa0;min protein |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | by the induction of ROS with regard to PMA and TNF-_amp_#x3b1 were 1_amp_#xa0;_amp_#x3bc;g/ml 1_amp_#xa0 _amp_#x3bc g ml or above and 5_amp_#xa0;ng/ml |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Effects of cilostazol on PMA or TNF-_amp_#x3b1 -induced glomerular ROS production PMA stimulation |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 stimulation |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | shown in Fig 7 100_amp_#xa0 _amp_#x3bc M of cilostazol suppressed TNF-_amp_#x3b1 -induced ROS production at 228 _amp_#xb1 7.76_amp_#xa0;counts/mg 7.76_amp_#xa0 counts mg |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | protein/20_amp_#xa0;min, protein 20_amp_#xa0 min which was approximately 81% of the TNF-_amp_#x3b1 -induced ROS production without cilostazol |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | no additive effects on the suppressive effects of cilostazol on TNF-_amp_#x3b1 -induced ROS production ( Fig 7 |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 0.9 | gp91-phox a component of NADPH oxidase and both gp91-phox and NOX4 are present in renal tissue especially proximal tubules ( Shiose |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 0.9 | NOX4 is also found in glomeruli and hyperglycemia upregulates its expression |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 has been reported to directly produce ROS in not only |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | The mechanism of NADPH oxidase activation by TNF-_amp_#x3b1 has not been fully elucidated |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | In addition TNF-_amp_#x3b1 has been shown to activate p47-phox an NADPH oxidase component |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Subsequently TNF-_amp_#x3b1 appears to activate NADPH oxidase via multiple signal transduction pathways |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | results of the present study using isolated glomeruli clarified that TNF-_amp_#x3b1 activates NADPH oxidase via PKC/PI-3 PKC PI-3 kinase and MAPK |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.4 | TNF-_amp_#x3b1 activates NADPH oxidase via PKC/PI-3 PKC PI-3 kinase and MAPK pathways ( Fig 8 |
| 9855 | RAP1A | RAP1A, member of RAS oncogene family | rap1a | 0.3 | on NADPH oxidase and Quilliam et al reported that when rap1a a GTP-binding protein was phosphorylated by PKA its affinity for |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | suppress NADPH oxidase activation in the presence of PMA or TNF-_amp_#x3b1 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | chemiluminescence responses of isolated glomeruli by PMA (a) a or TNF-_amp_#x3b1 (b), b and control (open open circle |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | _amp_#xb0 C before PMA (10_amp_#xa0;_amp_#x3bc;g/ml) 10_amp_#xa0 _amp_#x3bc g ml or TNF-_amp_#x3b1 (10_amp_#xa0;ng/ml) 10_amp_#xa0 ng ml was added |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | (b) b After addition of TNF-_amp_#x3b1 low and continuous chemiluminescence response was observed |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Fig 3._amp_#xa0 Effects of DPI H-7 wortmannin and SB203580 on TNF-_amp_#x3b1 -stimulated glomerous ROS production |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | N = 4 p _amp_#x3c 0.01 p _amp_#x3c 0.05 vs TNF-_amp_#x3b1 alone |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Fig 7._amp_#xa0 Effects of cilostazol on TNF-_amp_#x3b1 -stimulated glomerous ROS production |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 (10_amp_#xa0;ng/ml) 10_amp_#xa0 ng ml was added after a further 5_amp_#xa0 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | _amp_#xb1 SEM ( N = 4 p _amp_#x3c 0.05 vs TNF-_amp_#x3b1 alone |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 activates NADPH oxidase via both PKC- and MAPK-pathways. |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK-pathways. | 1.4 | TNF-_amp_#x3b1 activates NADPH oxidase via both PKC- and MAPK-pathways. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Cilostazol inhibits PMA- and TNF-_amp_#x3b1 -induced generation of superoxide probably by inhibiting the PI-3 kinase |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 1.4 | Abbreviations used are GTP guanosine 5_amp_#x2032 -triphosphate MAP mitogen-activated protein phox phagocyte oxidase PMA phorbol 12-myristate 13-acetate |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | constituent cells of the renal glomeruli have the capacity to release reactive oxygen species ros upon stimulation of nadph oxidase activated by protein kinase c pkc . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | constituent cells of the renal glomeruli have the capacity to release reactive oxygen species ros upon stimulation of nadph oxidase activated by protein kinase c pkc . |
| 6081 | INS | insulin | insulin | 1.0 | hyperglycemia and insulin resistance in the diabetic state are often associated with activation of pkc and tumor necrosis factor tnf _amp_#x3b1; respectively. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | hyperglycemia and insulin resistance in the diabetic state are often associated with activation of pkc and tumor necrosis factor tnf _amp_#x3b1; respectively. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the pkc inhibitor h 7 the nadph oxidase inhibitor diphenylene iodonium and the phosphatidylinositol 3 pi 3 kinase inhibitor wortmannin inhibited pma induced ros production by 100% 100% and 80% respectively. |
| 9391 | PRKAR2A | protein kinase, cAMP-dependent, regulatory, type II, alpha | protein kinase a | 1.0 | the phosphodiesterase inhibitor cilostazol activates protein kinase a and is reported to improve albuminuria in diabetic rats. |
| 11765 | TGFA | transforming growth factor, alpha | transforming growth factor | 1.0 | abnormalities such as increased blood flow in glomerular capillaries abnormal renal hemodynamics i.e. excessive filtration hostetter et al. 1981 elevated growth factor including transforming growth factor _amp_#x3b2;1 tgf _amp_#x3b2;1 hayashida and schnaper 2004 and advanced glycation endproducts ages vlassara et al. 1994 have been reported in the mesangial cells treated with high doses of glucose. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | increases in intracellular dag levels activate protein kinase c pkc inoguchi et al. 1992 a serine_amp_#x2013;threonine kinase and a study using neutrophils has shown that dag activates nadph oxidase via pkc activation fujita et al. 1984 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | increases in intracellular dag levels activate protein kinase c pkc inoguchi et al. 1992 a serine_amp_#x2013;threonine kinase and a study using neutrophils has shown that dag activates nadph oxidase via pkc activation fujita et al. 1984 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in the constituent cells of glomeruli nadph oxidase is present and these cells are capable of producing ros radeke et al. 1991 and greiber et al. 1998 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | hence it is possible that the hyperglycemia associated with diabetes stimulates nadph oxidase in glomeruli eliciting oxidative stress and is thus involved in the onset and progression of diabetic nephropathy. |
| 6081 | INS | insulin | insulin | 1.0 | activated macrophages secrete tumor necrosis factor _amp_#x3b1; tnf _amp_#x3b1; beutler et al. 1985 which is involved in the pathology of inflammation and insulin resistance. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | activated macrophages secrete tumor necrosis factor _amp_#x3b1; tnf _amp_#x3b1; beutler et al. 1985 which is involved in the pathology of inflammation and insulin resistance. |
| 399 | ALB | albumin | albumin | 1.0 | ieki used rats with streptozotocin stz induced diabetes and found that cilostazol a phosphodiesterase pde inhibitor lowered the excretion rate of urinary albumin which is an indicator of early stage diabetic nephropathy and that this mechanism involved increased na_amp_#x2013;k atpase activity via elevated camp levels in glomeruli ieki 1994 . |
| 6081 | INS | insulin | insulin | 1.0 | in order to test the above hypothesis the present study used isolated rat glomeruli to determine whether ros production is induced by tnf _amp_#x3b1; which is elevated by obesity and causes insulin resistance hotamisligil et al. 1993 or pma which stimulates hyperglycemia activated pkc. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to investigate glomerular signal transduction pathways one of the following compounds was added to the glomerulus culture solution at 5_amp_#xa0;min before pma stimulation: diphenylene iodonium an nadph oxidase specific inhibitor dpi dojindo laboratories kumamoto ; h 7 a pkc inhibitor [1 5 isoquinolinesulfonyl 2 methylpiperazine dihydrochloride biomol plymouth meeting usa]; wortmannin a phosphatidylinositol |
| 399 | ALB | albumin | serum albumin | 1.0 | glomerular protein levels were measured by the lowry method lowry et al. 1951 using bovine serum albumin to produce a standard curve. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in order to determine the mechanism of pma induced ros production the effects of dpi nadph oxidase inhibitor h 7 pkc inhibitor and wortmannin pi 3 kinase inhibitor on pma induced ros production were investigated. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it has been reported that glomerular ros production is mediated by nadph oxidase radeke et al. 1991 and that activation of glomerular nadph oxidase is involved in the pathology of chronic glomerulonephritis neale et al. 1993 and diabetic nephropathy onozato et al. 2002 . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in recent years studies have found that: there are multiple isoforms of nadph oxidase due to the polymorphism of gp91 phox a component of nadph oxidase and both gp91 phox and nox4 are present in renal tissue especially proximal tubules shiose et al. 2001 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in recent years studies have found that: there are multiple isoforms of nadph oxidase due to the polymorphism of gp91 phox a component of nadph oxidase and both gp91 phox and nox4 are present in renal tissue especially proximal tubules shiose et al. 2001 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | hyperglycemia is known to activate pkc via increased dag wolf et al. 1991 and it is thought that with pkc activation hyperglycemia itself activates nadph oxidase to accelerate oxidative stress. |
| 6081 | INS | insulin | insulin | 1.0 | the uptake of glucose in constituent cells of glomeruli except podocyte coward et al. 2005 is non insulin dependent and in diabetes glucose flows into the cells in hyperglycemia dependent manner. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | moreover in recent years since the involvement of nadph oxidase inhibition has been suggested as an action target shared by drugs such as angiotensin converting enzyme inhibitor and angiotensin receptor blocker onozato et al. 2002 which have been identified as be |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ngiotensin converting enzyme inhibitor and angiotensin receptor blocker onozato et al. 2002 which have been identified as being useful with respect to diabetic nephropathy we focused on the effect of nadph oxidase on renal glomeruli. |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | moreover in recent years since the involvement of nadph oxidase inhibition has been suggested as an action target shared by drugs such as angiotensin converting enzyme inhibitor and angiotensin receptor blocker onozato et al. 2002 which have been identified as being useful with respect to diabetic nephropathy we focused on the effect of nadph oxidase on renal glome |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | intracellular signal transduction for nadph oxidase activation in the constituent cells of glomeruli has not been clarified but in the present study wortmannin suppressed pma induced glomerular ros production by approximately 80% thus suggesting that |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | because nadph oxidase consists of multiple intracellular factors it is possible that there are multiple signal transduction pathways for each factor. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | therefore it is possible that even when stimulated by the same compound different cell types have different signal transduction pathways for nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the mechanism of nadph oxidase activation by tnf _amp_#x3b1; has not been fully elucidated. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in addition tnf _amp_#x3b1; has been shown to activate p47 phox an nadph oxidase component via the phosphorylation of p38map mitogen activated protein kinase benna et al. 1996 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | subsequently tnf _amp_#x3b1; appears to activate nadph oxidase via multiple signal transduction pathways. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the results of the present study using isolated glomeruli clarified that tnf _amp_#x3b1; activates nadph oxidase via pkc/pi 3 kinase and mapk pathways fig 8 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | hence the present study investigated the effects of cilostazol on glomerular ros production mediated by nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in addition it has also been reported that _amp_#x3b1; tocopherol inhibits nadph oxidase by suppressing pkc mediated phosphorylation and translocation of p47 phox cachia et al. 1998 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | from these findings we inferred that ca 2+ is involved in nadph oxidase activation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | studies have been conducted using neutrophils to determine the mechanism of the suppressive effects of camp on nadph oxidase and quilliam et al. reported that when rap1a a gtp binding protein was phosphorylated by pka its affinity for cytochrome b558 lowered thus inhibiting cytochrome b558 activation quilliam et al. 1991 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | using isolated glomeruli we investigated the inhibition site due to cilostazol on nadph oxidase suppression. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the above results suggest the involvement of pi 3 kinase in the activation of nadph oxidase in renal glomeruli thus we inferred that the inhibition levels of wortmannin and cilostazol are extremely close further downstream than pkc fig 8 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | as is the case with neutrophils the involvement of a pi 3 kinase dependent signal transduction pathway with nadph oxidase is suggested for glomerular ros production and pka may suppress glomerular nadph oxidase by hindering pi 3 kinase activation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | hence the suppressive effects of cilostazol on glomerular ros production originating from nadph oxidase were comparable to those of wortmannin a pi 3 kinase inhibitor. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings suggest that pkc activation stimulates nadph oxidase via a pi 3 kinase dependent pathway 80% and a pi 3 kinase independent pathway 20% to induce ros production; and that cilostazol inhibits pkc activity at the pi 3 kinase level to suppress nadph oxidas |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | via a pi 3 kinase dependent pathway 80% and a pi 3 kinase independent pathway 20% to induce ros production; and that cilostazol inhibits pkc activity at the pi 3 kinase level to suppress nadph oxidase activation in the presence of pma or tnf _amp_#x3b1;. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | fig. 8._amp_#xa0;possible signal transduction pathway to activate renal glomerular nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | pma induced activation of pkc activates nadph oxidase mainly via a pi 3 kinase pathway and partly via a pi 3 kinase independent pathway. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | tnf _amp_#x3b1; activates nadph oxidase via both pkc and mapk pathways. |