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16990215 ( ) |
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| Title | Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial arterioles in type 1 diabetes mellitus. |
| Abstract | OBJECTIVE: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). METHODS: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. RESULTS: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. CONCLUSIONS: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase. Medical Center, Omaha, 68198-5850, USA. wgmayhan@unmc.edu |
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 |
|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 21 | NOS-independent | NOS-dependent | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 18 | p47phox | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 14 | gp91phox | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 13 | p67phox | p67 phox | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 5 | angiotensin ii | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 3 | endothelial nitric oxide synthase | eNOS | |
| 11609 | TBXAS1 | thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) | 2 | cytochrome p450 | |
| 12805 | XDH | xanthine dehydrogenase | 2 | xanthine oxidase | |
| 2615 | CYP2B6 | cytochrome P450, family 2, subfamily B, polypeptide 6 | 2 | p450 | |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | 2 | p40phox | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 2 | angiotensin converting enzyme | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 2 | p22phox | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 7889 | NOX1 | NADPH oxidase 1 | 1 | Nox-1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent NOS -dependent (acetylcholine acetylcholine and adenosine diphosphate (ADP)) ADP and -independent |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | alter responses in nondiabetic rats apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | In addition p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | In addition p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | Conclusions The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the |
| 2615 | CYP2B6 | cytochrome P450, family 2, subfamily B, polypeptide 6 | p450 | 1.6 | arachidonic acid cascade (lipoxygenase lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase endothelial nitric oxide synthase (eNOS), eNOS and |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | cytochrome p450 system xanthine oxidase endothelial nitric oxide synthase (eNOS), eNOS and NADH/NAD(P)H NADH NAD P H oxidases |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.3 | a multicomponent enzyme complex that includes 2 membrane-associated subunits (p22phox p22phox and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | enzyme complex that includes 2 membrane-associated subunits (p22phox p22phox and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox p67 phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | p22phox and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox p67 phox and p40phox 10 17 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.3 | and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox p67 phox and p40phox 10 17 |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | p40phox | 1.3 | at least 3 cytosolic subunits (p47phox, p47phox p67 phox and p40phox 10 17 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | determine whether NAD(P)H NAD P H oxidase contributes to impaired NOS-dependent reactivity of pial arterioles during T1D |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | application of agonists that dilate cerebral arterioles via activation of NOS acetylcholine (1 1 and 10 M and 5'-adenosine diphosphate (ADP; |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-independent | 1.2 | We also examined responses of cerebral arterioles to a NOS-independent agonist nitroglycerin (1.0 1.0 and 10 M |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | measurement of NAD(P)H NAD P H oxidase subunits (nox-1, nox-1 p47phox and p67phox as described previously 47 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | NAD(P)H NAD P H oxidase subunits (nox-1, nox-1 p47phox and p67phox as described previously 47 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | for various subunits of NAD(P)H NAD P H oxidase (gp91phox, gp91phox p47phox and p67phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | various subunits of NAD(P)H NAD P H oxidase (gp91phox, gp91phox p47phox and p67phox |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | of NAD(P)H NAD P H oxidase (gp91phox, gp91phox p47phox and p67phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | performed using goat anti-NAD(P)H anti-NAD P H oxidase subunits (gp91phox, gp91phox nox-1 p47phox and p67phox (Santa Santa Cruz Biotechnology as the |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | goat anti-NAD(P)H anti-NAD P H oxidase subunits (gp91phox, gp91phox nox-1 p47phox and p67phox (Santa Santa Cruz Biotechnology as the primary antibody |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | anti-NAD P H oxidase subunits (gp91phox, gp91phox nox-1 p47phox and p67phox (Santa Santa Cruz Biotechnology as the primary antibody and peroxidase |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | Thus the effects of apocynin on NOS-dependent responses of cerebral arterioles in diabetic rats are not related |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | We found that T1D significantly upregulated gp91phox protein expression in parietal cortex tissue but did not influence |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | parietal cortex tissue but did not influence the expression of p47phox or p67phox protein in cortex tissue ( Figure 2 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | tissue but did not influence the expression of p47phox or p67phox protein in cortex tissue ( Figure 2 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | In addition we found that T1D significantly upregulated p47phox protein in cerebral microvessels but did not influence the expression |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.3 | but did not influence the expression of nox-1 protein or p67 phox protein in cerebral microvessels ( Figure 3 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | 3 _amp_#xa0 Enlarge Image Figure 2 Western blot analysis of gp91phox p47phox p67phox and tubulin proteins in parietal cortex of nondiabetic |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | _amp_#xa0 Enlarge Image Figure 2 Western blot analysis of gp91phox p47phox p67phox and tubulin proteins in parietal cortex of nondiabetic (open |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | Enlarge Image Figure 2 Western blot analysis of gp91phox p47phox p67phox and tubulin proteins in parietal cortex of nondiabetic (open open |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | _amp_#xa0 Enlarge Image Figure 3 Western blot analysis of nox-1 p47phox p67phox and tubulin proteins in cerebral microvessels of nondiabetic (open |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | Enlarge Image Figure 3 Western blot analysis of nox-1 p47phox p67phox and tubulin proteins in cerebral microvessels of nondiabetic (open open |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | First chronic treatment with apocynin alleviates T1D-induced impairment of NOS-dependent dilation of pial arterioles |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | Second T1D produces an upregulation in gp91phox protein in cortex tissue and p47phox protein in cerebral microvessels |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | produces an upregulation in gp91phox protein in cortex tissue and p47phox protein in cerebral microvessels |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | Based on these findings we suggest that impaired NOS-dependent dilation of pial arterioles in T1D is related to an |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | the role of NAD(P)H NAD P H oxidase in impaired NOS-dependent responses of pial arterioles in diabetic rats and biochemical studies |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | potential role for NAD(P)H NAD P H oxidase in impaired NOS-dependent responses of cerebral arterioles |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | NAD P H oxidase since it inhibits the translocation of p47phox |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | In the present study we found that apocynin alleviated impaired NOS-dependent reactivity of cerebral arterioles in diabetic rats and inhibited superoxide |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | of apocynin on vascular function appears to be specific for NOS-dependent agonists since treatment with apocynin did not alter responses to |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | Thus T1D specifically affects NOS-dependent reactivity |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | a determinant of vascular function then it should equally affect NOS-dependent and -independent reactivity of cerebral arterioles |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | In addition impaired NOS-dependent dilation of peripheral blood vessels 12 25 38 40 42 |
| 2615 | CYP2B6 | cytochrome P450, family 2, subfamily B, polypeptide 6 | p450 | 1.6 | arachidonic acid cascade (lipoxygenase lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase eNOS and NAD(P)H NAD P H oxidase |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase eNOS and NAD(P)H NAD P H oxidase |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.3 | a multicomponent enzyme complex that includes 2 membrane-associated subunits (p22phox p22phox and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | enzyme complex that includes 2 membrane-associated subunits (p22phox p22phox and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox p67phox and |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | p22phox and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox p67phox and p40phox 10 17 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | and gp91phox and at least 3 cytosolic subunits (p47phox, p47phox p67phox and p40phox 10 17 |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | p40phox | 1.3 | and at least 3 cytosolic subunits (p47phox, p47phox p67phox and p40phox 10 17 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | In addition although there may be several homologues of gp91phox 7 we elected to examine the influence of T1D on |
| 7889 | NOX1 | NADPH oxidase 1 | Nox-1 | 2.2 | Nox-1 has been identified in rat aortic smooth muscle cells (which |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | smooth muscle cells (which which contain relatively small amounts of gp91phox and appears to contribute to the production of reactive oxygen |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | NAD P H oxidase has been difficult it appears that p67phox must interact with gp91phox for the progression of oxidase activity |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | has been difficult it appears that p67phox must interact with gp91phox for the progression of oxidase activity |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | In addition it appears that a function of p47phox is to facilitate steady association of gp91phox and p67phox and |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | a function of p47phox is to facilitate steady association of gp91phox and p67phox and thus p47phox is critical for vascular NAD(P)H |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.3 | of p47phox is to facilitate steady association of gp91phox and p67phox and thus p47phox is critical for vascular NAD(P)H NAD P |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | to facilitate steady association of gp91phox and p67phox and thus p47phox is critical for vascular NAD(P)H NAD P H oxidase activation |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | Previous studies found that p47phox is upregulated during diseased states 2 6 8 24 41 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | In the present study we found an increase in gp91phox protein in the parietal cortex of diabetic rats and an |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | the parietal cortex of diabetic rats and an increase in p47phox protein in cerebral microvessels from diabetic rats |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | increases the activity of NAD(P)H NAD P H oxidase vascular p47phox expression and production of oxygen radicals 2 8 19 20 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | treatment of diabetic subjects with angiotensin-converting enzyme inhibitors improves impaired NOS-dependent responses of large peripheral blood vessels 11 39 and in |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | that treatment of diabetic rats with enalapril can alleviate impaired NOS-dependent responses of cerebral arterioles 48 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | of NAD(P)H NAD P H oxidase in T1D-induced impairment of NOS-dependent reactivity of pial arterioles |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 3.3 | of important subunits for NAD(P)H NAD P H oxidase (gp91phox gp91phox and p47phox were increased in diabetic rats |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.8 | subunits for NAD(P)H NAD P H oxidase (gp91phox gp91phox and p47phox were increased in diabetic rats |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | of NAD(P)H NAD P H oxidase alleviated T1D-induced impairment of NOS-dependent reactivity |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-dependent | 1.2 | activiation of NAD(P)H NAD P H oxidase contributes to impaired NOS-dependent dilation of pial arterioles during T1D |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | two to three months later the authors examined in vivo responses of pial arterioles to nitric oxide synthase nos dependent acetylcholine and adenosine diphosphate adp and independent nitroglycerin agonists. |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | s could contribute to vascular dysfunction in t1d including mitochondrial respiration the arachidonic acid cascade lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase endothelial nitric oxide synthase enos and nadh/nad p h oxidases. |
| 11609 | TBXAS1 | thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) | cytochrome p450 | 1.0 | to the production of superoxide and thus could contribute to vascular dysfunction in t1d including mitochondrial respiration the arachidonic acid cascade lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase endothelial nitric oxide synthase enos and nadh/nad p h oxidases. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | uperoxide and thus could contribute to vascular dysfunction in t1d including mitochondrial respiration the arachidonic acid cascade lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase endothelial nitric oxide synthase enos and nadh/nad p h oxidases. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | nad p h oxidase is a multicomponent enzyme complex that includes 2 membrane associated subunits p22phox and gp91phox and at least 3 cytosolic subunits p47phox p67 phox and p40phox [ 10 17 ]. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | in addition we found that t1d significantly upregulated p47phox protein in cerebral microvessels but did not influence the expression of nox 1 protein or p67 phox protein in cerebral microvessels figure 3 . |
| 11609 | TBXAS1 | thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) | cytochrome p450 | 1.0 | oduce superoxide and thus could potentially contribute to vascular dysfunction during t1d including mitochondrial respiration the arachidonic acid cascade lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase enos and nad p h oxidase. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | us could potentially contribute to vascular dysfunction during t1d including mitochondrial respiration the arachidonic acid cascade lipoxygenase and cyclooxygenase pathways the cytochrome p450 system xanthine oxidase enos and nad p h oxidase. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | one possibility is that angiotensin ii plays a critical role. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | stimulation of vascular smooth muscle cells with angiotensin ii thrombin lipopolysaccharide and cytokines increases the activity of nad p h oxidase vascular p47phox expression and production of oxygen radicals [ 2 8 19 20 21 30 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | in addition chronic hypertension induced synthesis/release of angiotensin ii stimulates oxygen radical formation via activation of nad p h oxidase [ 19 43 ]. |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | since tissue and plasma levels of angiotensin converting enzyme and thus angiotensin ii are elevated in diabetics [ 18 32 45 ] and since angiotensin ii has been shown to activate nad p h oxidase [ 20 43 ] it seems reasonable to suggest that the formation of super |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | since tissue and plasma levels of angiotensin converting enzyme and thus angiotensin ii are elevated in diabetics [ 18 32 45 ] and since angiotensin ii has been shown to activate nad p h oxidase [ 20 43 ] it seems reasonable to suggest that the formation of superoxide during t1d may be related to angiotensin ii induced stimulation of nad p h oxidase |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | has been shown to activate nad p h oxidase [ 20 43 ] it seems reasonable to suggest that the formation of superoxide during t1d may be related to angiotensin ii induced stimulation of nad p h oxidase. |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | support for this concept can be found in studies that report treatment of diabetic subjects with angiotensin converting enzyme inhibitors improves impaired nos dependent responses of large peripheral blood vessels [ 11 39 ] and in our study showing that treatment of diabetic rats with enalapril can alleviate impaired nos dep |