)| PMID |
15036821 ( ) |
|---|---|
| Title | p22phox-derived superoxide mediates enhanced proliferative capacity of diabetic vascular smooth muscle cells. |
| Abstract | To investigate the mechanisms that contribute to the acceleration of atherosclerosis in diabetes, the role of NAD(P)H oxidase in the enhanced proliferative capacity of diabetic vascular smooth muscle cells (VSMC) was studied. VSMC from streptozotocin (STZ)-induced diabetic rat aorta had increased proliferative capacity and generated higher levels of superoxide in comparison with cells from control rats. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated not only by tiron (1mM), a superoxide scavenger but also by diphenyleneiodonium (DPI; 10microM), an NAD(P)H oxidase inhibitor. Both the activity of NAD(P)H oxidase and p22phox expression were significantly increased in diabetic VSMC. Furthermore, inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide generation, which was accompanied by a significant attenuation of cell proliferation. Based on these results, it is suggested that diabetes-associated increase in NAD(P)H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats. Genetic Engineering, Pusan National University, 10 Ami-Dong 1-Ga, Seo-Gu, Busan 602-739, South Korea. |
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 |
|---|---|---|---|---|
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 31 | p22phox | |
| 12805 | XDH | xanthine dehydrogenase | 5 | xanthine oxidase | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 5 | SOD | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 2 | nitric oxide synthase | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 1 | p67phox | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91phox | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 1 | Rac | |
| 143 | ACTC1 | actin, alpha, cardiac muscle 1 | 1 | smooth muscle actin | |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | 1 | p40phox | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 1 | nadph oxidase | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | p47phox | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Both the activity of NAD(P)H NAD P H oxidase and p22phox expression were significantly increased in diabetic VSMC |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Furthermore inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Furthermore inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | NAD(P)H NAD P H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | gene polymorphism affecting at least one of the subunits (p22phox) p22phox has been linked to the development of atherosclerosis in humans |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | potential role of NAD(P)H NAD P H oxidase in particular p22phox in the enhanced proliferative capacity of diabetic VSMC was investigated |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | The PCR primers for amplification of p22phox mRNA were based on the published rat aortic smooth muscle |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | The sequences of oligonucleotides were as follows_amp_#x2014 sense p22phox 5_amp_#x2032 -GGTCCTCACCATGGGGCAGATC-3_amp_#x2032 and antisense p22phox 5_amp_#x2032 -GATCTGCCCCATGGTGAGGACC-3_amp_#x2032 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | oligonucleotides were as follows_amp_#x2014 sense p22phox 5_amp_#x2032 -GGTCCTCACCATGGGGCAGATC-3_amp_#x2032 and antisense p22phox 5_amp_#x2032 -GATCTGCCCCATGGTGAGGACC-3_amp_#x2032 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | In contrast to tiron SOD (500 500 units/ml), units ml which is not permeable to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | reduction in diabetic cells was not attenuated by treatment with SOD (500 500 units/ml) units ml |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Effect of p22phox antisense oligonucleotides on NBT reduction |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | intensity normalized to _amp_#x3b2 -actin revealed that the level of p22phox mRNA expression was higher in diabetic VSMC (62.5_amp_#xb1;8.2%) 62.5_amp_#xb1 8.2% |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | The expression of p22phox mRNA both in control and diabetic VSMC was substantially reduced |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | and diabetic VSMC was substantially reduced in cells transfected with p22phox antisense oligonucleotides compared to cells treated with vehicle or transfected |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | As shown in Fig 6 although inhibition of p22phox expression by antisense oligonucleotides was associated with the attenuated cellular |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Effect of p22phox antisense oligonucleotides on VSMC proliferation |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | analysis of the cell proliferation data revealed that inhibition of p22phox expression with antisense oligonucleotides was associated with a significant down-regulation |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | 2 the enhanced NADH oxidase activity was accompanied by increased p22phox expression in diabetic VSMC and (3) 3 both increased superoxide |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | cell proliferation in diabetic VSMC were reduced by transfection with p22phox antisense oligonucleotides |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | However the fact that SOD failed to inhibit FBS-stimulated cell proliferation both in control and |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | oxidase is a multisubunit complex with two membrane-associated subunits (p22phox p22phox and gp91phox and three cytosolic subunits (p40phox, p40phox p47phox and |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.0 | a multisubunit complex with two membrane-associated subunits (p22phox p22phox and gp91phox and three cytosolic subunits (p40phox, p40phox p47phox and p67phox regulated |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | p40phox | 1.3 | subunits (p22phox p22phox and gp91phox and three cytosolic subunits (p40phox, p40phox p47phox and p67phox regulated by Rac G proteins and this |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | (p22phox p22phox and gp91phox and three cytosolic subunits (p40phox, p40phox p47phox and p67phox regulated by Rac G proteins and this oxidase |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 1.3 | and gp91phox and three cytosolic subunits (p40phox, p40phox p47phox and p67phox regulated by Rac G proteins and this oxidase has been |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 0.0 | three cytosolic subunits (p40phox, p40phox p47phox and p67phox regulated by Rac G proteins and this oxidase has been previously identified in |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | role in signal transduction is to date only partially understood p22phox one of the electron transfer elements of NADH oxidase is |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | By using Northern blot analysis of p22phox mRNA expression in the aorta from type 2 diabetic rats |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | previous results in the present experiment the increased expression of p22phox mRNA in diabetic VSMC in association with enhanced superoxide production |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | superoxide production in diabetic VSMC was reduced by transfection of p22phox antisense oligonucleotides but not by sense oligonucleotides suggesting that p22phox |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | p22phox antisense oligonucleotides but not by sense oligonucleotides suggesting that p22phox is directly involved in NADH oxidase activity in diabetic VSMC |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Thus the data further support the involvement of p22phox subunit in superoxide production and VSMC proliferation in diabetic vasculature |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | increased NAD(P)H NAD P H oxidase activity via the enhanced p22phox expression |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | DPI (10 10 _amp_#x3bc M tiron (1 1 mM and SOD (500 500 units/ml) units ml on 10% FBS-stimulated cell proliferation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | as DPI (10 10 _amp_#x3bc M tiron (1 1 mM SOD (500 500 units/ml), units ml -NAME (10 10 _amp_#x3bc M |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Effect of transfection of p22phox antisense or sense oligonucleotides on the expression of p22phox mRNA |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | of p22phox antisense or sense oligonucleotides on the expression of p22phox mRNA in control and diabetic VSMC |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | (A) A Representative expression of p22phox mRNA by RT-PCR M molecular marker Veh vehicle AS antisense |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Effect of transfection of p22phox antisense or sense oligonucleotides on superoxide production in control and |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 4.0 | Effect of transfection of antisense or sense p22phox oligonucleotides on 10% FBS-induced cell proliferation in control and diabetic |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | among various potential sources of vascular superoxide production such as nad p h oxidases [ 14 ] xanthine oxidase [ 15 ] lipoxygenase mitochondrial oxidases and no synthases [ 16 ] nad p h oxidase is known as an important source of vascular superoxide production in animal models of diabetes [ 17 ]. |
| 143 | ACTC1 | actin, alpha, cardiac muscle 1 | smooth muscle actin | 1.0 | briefly vsmc exhibited a typical hill and valley growth pattern and also exhibited positive staining with antibody against _amp_#x3b1; smooth muscle actin but no staining with antibody against factor viii antigen. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | a buffer blank containing lucigenin was subtracted _amp_#x3c;5% of the cell signal from each reading before transformation of the data by comparison with standard curve generated with xanthine/xanthine oxidase. 2.6. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | neither name 10 _amp_#x3bc;m a nitric oxide synthase inhibitor nor allopurinol 10 _amp_#x3bc;m a xanthine oxidase inhibitor significantly decreased nbt reduction in diabetic vsmc. 3.4. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | neither name 10 _amp_#x3bc;m a nitric oxide synthase inhibitor nor allopurinol 10 _amp_#x3bc;m a xanthine oxidase inhibitor significantly decreased nbt reduction in diabetic vsmc. 3.4. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | among various sources of vascular superoxide such as nad p h oxidases xanthine oxidase lipoxygenase mitochondrial oxidases and no synthases [ 14 15 and 16 ] nad p h oxidase appears to be the principal source of superoxide in several animal models of vascular diseases including diabetes |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | the enhanced superoxide production in diabetic vsmc was markedly reduced by treatment with dpi but not by inhibitors for other oxidases such as xanthine oxidase and nitric oxide synthase suggesting that nad p h oxidase is involved in the enhanced production of superoxide in diabetic vsmc. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the enhanced superoxide production in diabetic vsmc was markedly reduced by treatment with dpi but not by inhibitors for other oxidases such as xanthine oxidase and nitric oxide synthase suggesting that nad p h oxidase is involved in the enhanced production of superoxide in diabetic vsmc. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | dna primers|membrane transport proteins|oligonucleotides antisense|phosphoproteins|superoxides|nad|xanthine|nadh nadph oxidoreductases|cyba protein human|nadph oxidase|nadph dehydrogenase| |