Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury
2014
Ischemia/
reperfusion injuryis 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 injuryremains 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-2′-
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 necrosisin 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 necrosisin the kidney.
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