Abstract
Renal ischemia-reperfusion (I/R) injury is characterized by elevated expression of homocysteine and decreased production of hydrogen sulfide (H(2)S). Cystathionine γ-lyase (CSE) is a key factor in the onset of renal I/R injury, while IFC-305 can regulate the expression of CSE via epigenetic modification. Animal and cellular models of I/R were established in this work, followed by H&E staining to evaluate the extent of renal tissue injury under distinct conditions. Several methods, including ELISA, qPCR and Western blot, were used to analyze the levels of creatinine, CSE and H(2)S in various I/R models. Bisulfite sequencing PCR was used to evaluate the level of DNA methylation. The severity of the renal injury was significantly elevated in I/R rats and alleviated by the IFC-305 treatment. The level of Hcy was increased in the renal tissue and peripheral blood of I/R rats, while the IFC-305 treatment inhibited the expression of homocysteine (Hcy). Mechanistically, the DNA methylation in the CSE promoter was dramatically enhanced in I/R rats and cells, while the IFC-305 treatment reduced the level of DNA methylation in the CSE promoter. Moreover, the IFC-305 increased the concentration of H(2)S, which was reduced in I/R rats and cells. Finally, I/R rats and cells showed aberrantly high levels of MDA and superoxide, while the IFC-305 treatment reduced the levels of malondialdehyde (MDA) and superoxide. IFC-305, an adenosine derivative, promoted the production of H(2)S and attenuated renal injury in cellular and animal models of renal I/R by modifying the methylation status of the CSE promoter.