Renal ischemia-reperfusion injury (IRI) is a common course of acute kidney injury. We have found that glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1) is upregulated in kidney of wild type mice but not of hypoxia-inducible factor-1alpha heterozygous knockout (hKO) mice during IRI. Since CHAC1 is an inducer of apoptosis, we investigated apoptotic induction in kidneys during IRI. Apoptotic cells in the kidney of wild type mice are induced 12-h after ischemia/reperfusion treatment. In contrast, the induction of apoptotic cells in hKO mice was retarded. The ratio of anti-apoptotic Bcl-2 (B-cell lymphoma 2)/pro-apoptotic Bax (Bcl-2 associated X) was increased in hKO mice, indicating that dysregulation of Bcl-2 and/or BAX by CHAC1 participates in retardation of apoptotic induction in hKO mice kidney. In addition, CHAC1 knockdown with siRNA in HK2 cells, a human renal proximal tubule cell line, observed increased expression of Bcl-2 but not Bax. CHAC1 knockdown also increased intracellular glutathione concentration in HK2. Since a previous report showed the expression levels of Bcl-2 are correlated with cellular glutathione concentration, CHAC1 probably regulates Bcl-2 expression or apoptotic induction through regulation of glutathione concentration in IRI.

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