Sautin Yuri Y, Nakagawa Takahiko, Zharikov Sergey, Johnson Richard J
Division of Nephrology, Hypertension, and Transplantation, Dept of Medicine, University of Florida, Gainesville, FL 32610-0224, USA.
Am J Physiol Cell Physiol. 2007 Aug;293(2):C584-96. doi: 10.1152/ajpcell.00600.2006. Epub 2007 Apr 11.
Uric acid is considered a major antioxidant in human blood that may protect against aging and oxidative stress. Despite its proposed protective properties, elevated levels of uric acid are commonly associated with increased risk for cardiovascular disease and mortality. Furthermore, recent experimental studies suggest that uric acid may have a causal role in hypertension and metabolic syndrome. All these conditions are thought to be mediated by oxidative stress. In this study we demonstrate that differentiation of cultured mouse adipocytes is associated with increased production of reactive oxygen species (ROS) and uptake of uric acid. Soluble uric acid stimulated an increase in NADPH oxidase activity and ROS production in mature adipocytes but not in preadipocytes. The stimulation of NADPH oxidase-dependent ROS by uric acid resulted in activation of MAP kinases p38 and ERK1/2, a decrease in nitric oxide bioavailability, and an increase in protein nitrosylation and lipid oxidation. Collectively, our results suggest that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. Since oxidative stress in the adipose tissue has recently been recognized as a major cause of insulin resistance and cardiovascular disease, hyperuricemia-induced alterations in oxidative homeostasis in the adipose tissue might play an important role in these derangements.
尿酸被认为是人体血液中的一种主要抗氧化剂，可能预防衰老和氧化应激。尽管有其所谓的保护特性，但尿酸水平升高通常与心血管疾病风险增加和死亡率相关。此外，最近的实验研究表明，尿酸可能在高血压和代谢综合征中起因果作用。所有这些情况都被认为是由氧化应激介导的。在本研究中，我们证明培养的小鼠脂肪细胞分化与活性氧（ROS）产生增加和尿酸摄取有关。可溶性尿酸刺激成熟脂肪细胞中NADPH氧化酶活性增加和ROS产生，但对前脂肪细胞无此作用。尿酸对NADPH氧化酶依赖性ROS的刺激导致丝裂原活化蛋白激酶p38和ERK1/2激活、一氧化氮生物利用度降低、蛋白质亚硝化和脂质氧化增加。总体而言，我们的结果表明高尿酸血症在脂肪细胞中诱导氧化还原依赖性信号传导和氧化应激。由于脂肪组织中的氧化应激最近被认为是胰岛素抵抗和心血管疾病的主要原因，高尿酸血症引起的脂肪组织氧化稳态改变可能在这些紊乱中起重要作用。
