p22phox C242T gene polymorphism and overt diabetic nephropathy: a meta-analysis of 1,452 participants

BACKGROUND/AIMS: The p22phox C242T gene polymorphism (rs4673) may be linked to an increased susceptibility for overt diabetic nephropathy (ODN), but the study results are still inconclusive. METHODS: To explore the relationship between p22phox C242T gene polymorphism and ODN, the current meta-analysis of 707 ODN patients and 745 controls from five individual studies was conducted. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were evaluated by either a random or fixed effect model. RESULTS: In our meta-analysis, a significant relationship between the p22phox C242T gene polymorphism and ODN was found under allelic (OR, 2.760; 95% CI, 1.400 to 5.450; p = 0.004), recessive (OR, 5.080; 95% CI, 1.020 to 25.430; p = 0.05), dominant (OR, 1.700; 95% CI, 1.167 to 2.477; p = 0.006), homozygous (OR, 3.900; 95% CI, 1.022 to 14.889; p = 0.046), heterozygous (OR, 1.523; 95% CI, 1.167 to 1.986; p = 0.002), and additive genetic models (OR, 2.019; 95% CI, 1.232 to 3.309; p = 0.005). CONCLUSIONS: A positive correlation between p22phox C242T gene polymorphism and ODN risk was found. The T allele carriers of p22phox C242T gene polymorphism might be predisposed to ODN.

Identification of Nef-HIV-1 domains involved in p22-phox interaction and superoxide production / Identificación del dominio de Nef-VIH-1 involucrado en la interacción con p22-phox y producción de superoxido

Nef -HIV-1 has been shown to be involved in NADPH complex interaction and superoxide production. The aim of this work was to study the domains involved in the interaction between Nef and p22-phox. Two approaches were used: 1) in silico modelling, to determine the potential binding motifs and design Nef truncated forms and 2) functional assays. The results showed that GFPVT 68-72, FPDW 121-124 and REVLE 179-183 on Nef are critical for p22-phox (RPQIG 142-146 and PGGP 181-184) docking. However, only the region containing FPDW 121-124 on Nef is able to induce superoxide production. Understanding the molecular mechanisms involved in generating oxidative stress during HIV infection, is critical for therapeutic intervention, in order to minimize viral replication and dissemination.

Se ha evidenciado que Nef-VIH-1 está involucrado en la interacción con el complejo NADPH y la producción de superóxido. El objetivo de este trabajo fue identificar los dominios implicados en la interacción entre Nef y p22-phox. Se utilizaron dos estrategias: 1) análisis in silico para determinar los posibles motivos de unión y el diseño Nef formas truncadas y 2) ensayos funcionales. Los resultados mostraron que GFPVT 68-72, FPDW 121 a 124 y 179 a 183 REVLE de Nef son críticos para su unión con p22-phox (RPQIG 142-146 y 181-184 PGGP). Sin embargo, sólo la región que contiene FPDW 121-124 en Nef, es capaz de inducir la producción de superóxido. La comprensión de los mecanismos moleculares implicados en la generación de estrés oxidativo durante la infección por VIH, es crítico para la intervención terapéutica, con el fin de minimizar la replicación y la propagación viral.

Genistein antagonizes paraoxon-induced high expressions of NADPH oxidase p22phox and Nox4 in rat thoracic aorta tissues / 中国药理学通报

Aim To investigate whether genistein pro-tects paraoxon-induced vascular endothelial dysfunction through down-regulating p22phox and Nox4 expressions as well as inhibiting the generation of ROS.Methods In this study,thoracic aortas were isolated from the male Sprague-Dawley(SD)rats and were divided into the following groups:① control group,the thoracic a-ortas were incubated with dimethyl sulfoxide (DMSO, 0.1%)for 30 min;② genistein group,the thoracic a-ortas were incubated with genistein(100 μmol·L -1 ) for 30 min;③ paraoxon group,the thoracic aortas were incubated with paraoxon at the concentration of 40.5 μmol · L -1 for 30 min; ④ paraoxon plus genistein groups,the thoracic aortas were incubated with paraoxon (40.5 μmol·L -1 )plus genistein (100μmol·L -1 )for 30 min.The expressions of p22phox and Nox4 mRNA were detected by RT-PCR and the protein expressions ofp 2 2 phox and Nox4 were detected by Western blot.Results Compared with the control group,the expressions of p22phox and Nox4 were markedly increased in the paraoxon group. In the genistein group,the expressions of p22phox and Nox4 were significantly repressed. When treated with genistein plus paraoxon,there was a marked increase in the expression of Nox4(P <0.05),but no signifi-cant difference in the expression of p22phox.The ex-pression of p22phox in the paraoxon plus genistein group was significantly decreased(P <0.05)as com-pared with paraoxin group,but there was no significant difference in the expression of Nox4.Conclusion Paraoxon may result in oxidative damage of vascular endothelium through up-regulating p22phox and Nox4 expressions,genistein may down-regulate the expres-sions of both and protect vascular endothelium.

Correlation of NADPH oxidase subunit p22phox gene C242T polymorphism with left ventricular hypertrophy in Chinese Korean hypertensive patients / 实用医学杂志

Objective To investigate the relation between the NOSP gene C242T polymorphism and Chinese Korean nationality EH patients with LVH. Methods 108 Chinese Korean controls and 231 Chinese Korean EH patients were enrolled in the research.NOSP gene C242T polymorphism was analyzed by PCR. EH patients were divided into EH and EH+LVH group,all of them were evaluated with CDUS for left ventricular mass index. Results The distribution of NOSP gene C242T polymorphism showed no significant difference compared with controls and EH group.There was significant difference in distribution of CC vs CT+TT genotype between EH and EH+ LVH patients.CC genotype is more dangerous for EH patients combined with LVH than CT and TT genotypes. Conclusions The NOSP gene C242T polymorphism has no relation with EH in Korean nationality people. The NOSP gene C242T polymorphism has relation with EH+LVH; and the CC genotype is a susceptible gene for the Korean EH patients with LVH.

Chronic Granulomatous Disease on Jeju Island, Korea

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in p22phox). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.

Effects of Recombinant Angiotensin-converting enzyme 2 Gene on Oxidative Stress Levels in Human Endothelial Cells / 中华高血压杂志

Backgroup and objective Angiotensin-converting enzyme 2 (ACE2) is the first known homologue of human ACE gene up till now,however,its regulatory role in oxidative stress remains unclear.Our aim is to in- vestigate the effects of recombinant ACE2 gene transfer on the expression of p22~(phox),a key subunit of NADPH oxi- dase,and malonyldialdehyde (MDA) levels induced by angiotension(Ang) Ⅱ in cultured human endothelial cells. Methods A recombinant plasmid encompassing human ACE2 gene (pACE2) was constructed and transfected into these cells.The mRNA and protein levels of p22~(phox) in endothelial cells were determined by real-time PCR and Western blotting,respectively.MDA contents were measured by thiobarbiturie acid colorimetrie method in cells. Results The mRNA and protein expressions of p22~(phox) were drastically enhanced after exposures of endothelial cells to Ang Ⅱ(100 nmol/L) and Ang Ⅳ(100 nmol/L),accompanied by an increase in MDA contents (n=6,P

Tempol Improved Aortic Remodeling in Renovascular Hypertensive Rats / 中华高血压杂志

Background Mitochondria are the primary sites for ROS production within cells,Tempol(4-Hydroxy 2,2,6,6,tetramethyl piperidine)is a classic compounds targeting ROS scavengers in mitochondria.Objective To investigate the effects of Tempol on aortic function and remodeling in renovascular hypertensive rats.Methods The 2 kindey 1 clip hypertensive model was established in 24 male Wista rats and randomized to untreated hypertensive rats(n=6) or treated with Tempol(1 mmol/L) in drinking water(n=6) for 8 weeks.BP blood plasma angiotensinⅡ(AngⅡ),nitric oxide(NO),8-iso-PGF_(2?) level were determined.Isometric tension change of aortic rings were recorded;RT-PCR were used to measure the expression of NADPH p22 phox mRNA of aorta.Results Hypertensive rats had highter BP,AngⅡ,8-iso-PGF_(2?),media wall,media wall/lumen(W/L)(P

Benazepril and Candesartan Attenuate Oxidative Stress in Aorta in Spontaneously Hypertensive Rats / 中华高血压杂志

Objective To study the anti-oxidative stress effects of benazepril and candesartan.Methods SHRs of 12 weeks old were given benazepril(10 mg/kg?d,n=9)or candesartan(4 mg/kg?d,n=9)or combina- tion(Ben:10 mg/kg?d+Can:4 mg/kg?d)for 12 weeks.The tail arterial pressure was measured every two weeks.At end of study,pathological changes in the thoracic aorta,activity of SOD,serum contents of NO and hydroxy radicals,plasma Ang Ⅱ and cGMP,eNOS and P22~(phox)protein expressions in aortic tunica intima were de- termined.Results The thoracic aorta wall was thickened markedly in SHRs,and blood pressure,hydroxy radi- cal,Ang Ⅱ and P22~(phox)protein expression were increased significantly,while the serum NO,level of cGMP and eNOS expression were decreased.Benazepril(Ben)or Candesartan(Can)inhibit the thickening of vessel wall, enhance the activity of SOD(Ben:68.7?2.1,Can:65.6?4.2 vs SHR:48.8?3.2 U/mL,P

Effect of Radix Paeoniae Bubra on NADPH oxidase p22phox,MCP-1 mRNA expression and neointimal hyperplasia after balloon injury in cholesterol-fed rabbits / 中华中医药杂志

Objective:To observe the effect of Radix Paeoniae Bubra(RPB)on NADPH oxidase p22phox,monocyte chemotactic protein-1(MCP-1)mRNA expression and neointimal hyperplasia after carotid artery balloon injury in cholesterol-fed rabbits.Methods:The rabbit model of carotid balloon injury was established adopting Clowes method,and treated with extract of RPB.Component of neointima and expression of proliferating cell nuclear antigen(PCNA)and macrophage was determined by immunochemical stain.The collagen of typeⅠwas detected by special staining for blood vessels and the area of neointima was measured by image assay system.Expression of NADPH oxidase p22phox mRNA,MCP-1 mRNA was detected by in situ hybridization and transcription-polymerase chain reaction.Results:RPB can attenuate the neointima area and proliferation of collagen typeⅠinduced by balloon-injury,remarkable prevent the formation of restenosi,and down-regulate expression of NADPH oxidase p22 and MCP-1mRNA significantly and decrease the degree of macrophages infiltration especially in vessel wall of injuring carotid artery.Conclusions:RPB inhibited NADPH oxidase P22Phox and MCP-1 mRNA expression,and modestly reduced neointimal hyperplasia,which might be partly attributed to its antioxidant and inflammatory effects.