Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury

作者：Nakayama Yosuke^*; Ueda Seiji; Yamagishi Sho ichi; Obara Nana; Taguchi Kensei; Ando Ryotaro; Kaida Yusuke; Iwatani Ryuji; Kaifu Kumiko; Yokoro Miyuki; Toyonaga Maki; Kusumoto Takuo; Fukami Kei; Okuda Seiya

来源：Kidney International, 2014, 85(3): 570-578.

DOI：10.1038/ki.2013.398

• ADMA
• DDAH-1
• ischemia/reperfusion injury
• oxidative stress
• renal capillary loss

Ischemia/reperfusion injury is the leading cause of acute tubular necrosis. Nitric oxide has a protective role against ischemia/reperfusion injury; however, the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced by protein arginine methyltransferase (PRMT) and is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Here we examined the kinetics of ADMA and PRMT and DDAH expression in the kidneys of ischemia/reperfusion-injured mice. After the injury, DDAH-1 levels were decreased and renal and plasma ADMA values were increased in association with renal dysfunction. Renal ADMA was correlated with 8-hydroxy-20-deoxyguanosine, a marker of oxidative stress. An antioxidant, N-acetylcysteine, or a proteasomal inhibitor, MG-132, restored these alterations. Infusion of subpressor dose of ADMA exacerbated renal dysfunction, capillary loss, and tubular necrosis in the kidneys of ischemia/reperfusion-injured wild mice, while damage was attenuated in DDAH transgenic mice. Thus, ischemia/reperfusion injury-induced oxidative stress may reduce DDAH expression and cause ADMA accumulation, which may contribute to capillary loss and tubular necrosis in the kidney.

• 出版日期2014-3