Disease relevance of Cyba

• An increase in p22phox is required for increased renal NADPH oxidase activity, expression of Nox proteins and oxidative stress, and contributes < or =50% to hypertension during an Ang II slow-pressor response [1].
• Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases after myocardial infarction [2].
• Here, we examine the pathways leading to oxidase activation, and demonstrate that arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based NADH/NADPH oxidase [3].
• In the aorta from old OLETF rat with hyperglycemia, the enhanced NADH oxidase activity in association with upregulated expression of p22phox and gp91phox was observed, but not in both LETO and young (10 weeks) OLETF rats without hyperglycemia [4].

High impact information on Cyba

• Immunohistochemical staining indicated the localization of NADPH oxidase proteins gp91phox, p22phox, p47phox, and p67phox almost exclusively in the adventitia of the rat aorta with no substantial staining in the media [5].
• p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats [6].
• To investigate the mechanism responsible for this increased oxidase activity, we examined p22phox mRNA expression in rats made hypertensive by implanting an osmotic minipump that delivered Ang II (0.7 mg/kg per day) [6].
• In situ hybridization of aortic tissue showed that p22phox mRNA was expressed in medial smooth muscle as well as in the adventitia [6].
• These findings suggest that Ang II-induced hypertension activates the NADPH/NADH oxidase system by upregulating mRNA levels of one or several components of this oxidase system, including the p22phox, and that the NADPH/NADH oxidase system is associated with the pathology of hypertension in vivo [6].

Chemical compound and disease context of Cyba

• In parallel, hypertension did not affect the expression of p22phox, a component of the free radical generating enzyme reduced nicotinamide adenine dinucleotide phosphate oxidase [7].

Biological context of Cyba

• RNA silencing in vivo reveals role of p22phox in rat angiotensin slow pressor response [1].
• Here we report the isolation and nucleotide sequence of a cDNA for the cytochrome b-558 alpha-subunit of the NADPH oxidase in rat vascular smooth muscle cells (VSMCs) [8].
• Inhibition of nascent protein synthesis by a translation inhibitor, cycloheximide, significantly reduced p22-phox mRNA stability in proliferating but not in confluent CMEC [9].
• 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 [10].
• Furthermore, infusion of recombinant heparin-binding superoxide dismutase decreased both blood pressure and p22phox mRNA expression [6].

Anatomical context of Cyba

• Two siRNA sequences to p22phox (sip22phox) reduced mRNA >85% in cultured vascular smooth muscle cells [1].
• Cytochrome b-558 alpha-subunit cloning and expression in rat aortic smooth muscle cells [8].
• In both groups, sip22phox, relative to control siRNA, led to significant (P<0.001; approximately 50%) reductions in expression of p22phox mRNA and protein and of NADPH oxidase activity in the kidney cortex [1].
• Coronary microvascular endothelial cell growth regulates expression of the gene encoding p22-phox [9].
• An NADPH-oxidase complex containing at least two protein components (gp91-phox and p22-phox) and a unique low redox potential (-245 mV) cytochrome b-245 is the source of superoxide generated for bacterial killing in neutrophils and has been suggested as the oxygen sensor in the carotid body [11].

Associations of Cyba with chemical compounds

• This study shows greater levels of p22-phox mRNA/protein expression, NAD(P)H oxidase activity, and superoxide anion (O(2)(-)) production in proliferating versus fully confluent and growth-arrested 50% confluent CMEC [9].
• Both enhanced transcription of the p22-phox gene and enhanced mRNA half-life were shown to contribute to the increase in p22-phox mRNA levels as demonstrated by nuclear run-on studies and Northern analyses after actinomycin D transcriptional arrest, respectively [9].
• The increases in p22-phox mRNA levels induced by a stretch force in combination with angiotensin II were prevented by treatment with an angiotensin type I (AT1) receptor antagonist, RNH-6270 (100 nmol/l) [12].
• To this end, first we examined the abundance of several components of reduced nicotinamide-adenine dinucleotide phosphate oxidase (identified as the major source of reactive oxygen species), including gp91phox/Nox2, p22phox, p47phox, and Nox3 using real-time PCR [13].
• Cells were transiently transfected with phosphorothioate-modified rat p22phox antisense oligonucleotides to investigate the potential role of NAD(P)H oxidase [14].

Physical interactions of Cyba

• We conclude adult CF express Nox4/p22 phox-containing oxidant generating complex activated by H(2)O(2), OAG, and AA through a pathway that requires activation of PLA(2) [15].

Regulatory relationships of Cyba

• This effect was transduced by angiotensin receptor type-1 (AT1) and was inhibited by a flavoprotein inhibitor (DIP) or p22phox antisense oligonucleotides, indicating the involvement of membrane NAD(P)H oxidase [14].
• Antisense against p22phox also solely inhibited p38 MAPK but did not affect ERK [16].

Other interactions of Cyba

• We used double-stranded interfering RNAs (siRNAs) in Sprague Dawley rats in vivo to test the hypothesis that an increase in the p22phox component of NADPH oxidase is required for this response [1].
• The aortic expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox1, Nox2, Nox4, and p22phox) was higher in SHR compared with WKY [17].
• Genistein thus appears to act as an antioxidant at the transcription level by the downregulation of p22phox and AT1 receptor expression [18].
• In addition, prolonged treatment with TNF-alpha increased p22phox mRNA expression without affecting p22phox mRNA stability, and only when transcriptional activity was intact [19].
• Expression of p22-phox, the major membrane subunit of NADPH oxidase, and MCP-1 was augmented in cuff-injured adventitia of the Control but not the thermal-treated groups [20].

Analytical, diagnostic and therapeutic context of Cyba

• Western blots with plasma membrane-enriched fractions of cell lysate detected elevated levels of p22phox, p67phox, and rac-1, which indicates increased oxidase assembly [21].
• Furthermore, higher gp91phox and p22phox mRNA expression, measured by quantitative real-time RT-PCR, was found in the cocaine group [22].
• Expression of p22phox mRNA after Ang II-treatment was detected with Northern blots [14].
• After 8 weeks, superoxide levels in carotid arteries and aortas were measured by lucigenin chemiluminescence and p22phox expression quantified by immunohistochemistry [23].
• Myocardial content of nitrotyrosine, nitric oxide synthase (NOS) isoforms, and phagocyte-type NAD(P)H-oxidase subunits (p67-phox and p22-phox) were analyzed by immunoblotting and immunohistochemistry assays [24].

References