Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and the opposing effect of L-arginine
Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and the opposing effect of L-arginine
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DOI：
10.1096/fj.02-0585com
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Igarashi, J
中科院分区：
文献类型：
--
作者：
Kosaka, H;Yoneyama, H;Igarashi, J
凝集素样氧化型低密度脂蛋白受体(LOX-1)是新近发现的内皮细胞表面氧化修饰低密度脂蛋白的主要受体。器官移植后供体器官的关节硬化进展是一个主要问题。我们假设缺血再灌流诱导LOX-1。双侧肾缺血1h再灌注3h、6h、12h后，首次发现再灌注6h肾皮质和髓质LOX-1mRNA表达增加，补充L精氨酸后，LOX-1mRNA表达降低。再灌流6h后，血浆一氧化氮终末产物亚硝酸盐和硝酸盐含量及诱导型一氧化氮合酶表达均增加，而一氧化氮合酶底物L精氨酸可抑制肾组织诱导型一氧化氮合酶的表达，而不增加血浆一氧化氮终末产物含量。我们假设可用L精氨酸在缺血再灌流中被耗尽，导致诱导型一氧化氮合酶的诱导。缺血再灌注早期肾组织L-精氨酸水平降低，L-精氨酸补充组肾皮质NO终末产物增加。这些结果首次揭示了缺血再灌注所致的L精氨酸缺乏可引起结构性一氧化氮合酶的解偶联，从而诱导诱导型一氧化氮合酶和LOX-1，提示L精氨酸对卒中或移植有有效的预防动脉粥样硬化进展的作用。
Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a newly identified endothelial cell surface major receptor for oxidatively modified low-density lipoprotein. Progression of arthrosclerosis in the donor organ after organ transplantation is a major problem. We hypothesized that ischemia-reperfusion induces LOX-1. After 1 h ischemia of bilateral kidneys plus 3, 6, or 12 h reperfusion, we first revealed that LOX-1 mRNA expression was increased in renal cortex and medulla at 6 h after reperfusion, which was decreased by L-arginine supplement. Plasma nitric oxide (NO) end-product nitrite plus nitrate and inducible nitric oxide synthase (NOS) expression were increased after reperfusion of 6 h. However, NOS substrate L-arginine did not augment but markedly decreased plasma NO end product, because L-arginine supplement suppressed inducible NOS expression in kidney. We hypothesized that available L-arginine is depleted by ischemia-reperfusion, leading to inducible NOS induction. Ischemia decreased L-arginine levels in kidney and L-arginine supplement increased NO end products in renal cortex in the earliest phase of reperfusion. These results disclosed for the first time that a deficiency in L-arginine by ischemia reperfusion causes uncoupling of constitutive NOS, which induces inducible NOS and LOX-1, implying why L-arginine is effective for stroke or transplantation in preventing atherosclerotic progress.