Salt intake, oxidative stress, and renal expression of NADPH oxidase and superoxide dismutase
Salt intake, oxidative stress, and renal expression of NADPH oxidase and superoxide dismutase
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DOI：
10.1097/01.asn.0000092145.90389.65
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发表时间：
2003-11-01
影响因子：
13.6
通讯作者：
Wilcox, CS
中科院分区：
文献类型：
--
作者：
Kitiyakara, C;Chabrashvili, T;Wilcox, CS
研究了高盐 (HS) 摄入会增加氧化应激的假设，该假设与 NAD(P)H 氧化酶和超氧化物歧化酶 (SOD) 的肾皮质表达有关。在低盐、正常盐或 HS 饮食期间，在清醒大鼠组（n = 6 至 8）中测量 8-异前列烷 PGF(2α) 和丙二醛。通过化学发光评估 NADPH 和 NADH 刺激的超氧阴离子 (O-2(-)) 生成，并通过实时 PCR 评估 NAD(P)H 氧化酶和 SOD 的表达。随着盐摄入量的增加，8-异前列腺素和丙二醛的排泄量增加了两到三倍（P<0.001），而前列腺素E-2则没有变化。随着盐的摄入，肾皮质 NADH- 和 NADPH- 刺激的 O-2(-) 生成增加 (P < 0.05) 30% 至 40%。与低盐饮食相比，HS显着（P < 0.005）增加肾皮质gp91（phox）和P47（phox）mRNA的表达，并降低细胞内CuZn（IC）-SOD和线粒体（Mn）-SOD的表达。尽管肾素-血管紧张素系统受到抑制，盐负荷仍会增强氧化应激。这伴随着肾皮质 NADH 和 NADPH 氧化酶活性的增加以及 gp91(phox) 和 P47(phox) 表达的增加以及 IC- 和 Mn-SOD 的减少。因此，盐的摄入增强了O-2(-)的生成，同时增强了肾表达和NAD(P)H氧化酶的活性，同时降低了IC-和Mn-SOD的肾表达。
The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF(2alpha) and malonyldialdehyde were measured in groups (n = 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH- and NADH-stimulated superoxide anion (O-2(-)) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-iso-prostane and malonyldialdehyde increased incrementally two-to threefold with salt intake (P < 0.001), whereas prostaglandin E-2 was unchanged. Renal cortical NADH- and NADPH- stimulable O-2(-) generation increased (P < 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P < 0.005) increased renal cortical mRNA expression of gp91(phox) and P47(phox) and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91(phox) and P47(phox) and decreased IC- and Mn-SOD. Thus, salt intake enhances generation of O-2(-) accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC- and Mn-SOD.