Cilostazol protects against myocardial ischemia and reperfusion injury by activating transcription factor EB (TFEB)

In this study, a rat model of I/R injury was constructed and quantitative real ‐time PCR, Western blot, and immunofluorescence (IF) assay were performed. Our results showed that cilostazol increased LC3 II/LC3 I ratio, reduced p62 abundance, and promoted the expressions of LAMP1, LAMP2, cathepsin B, and cathepsin D, indicating that cilostazol could activate autophagy and ele vated lysosome activation. Following analysis showed that cilostazol enhanced nuclear protein expression of transcription factor EB (TFEB), an important regulator of autophagy‐lysosome pathway. Furthermore, CCI‐779, an inhibitor of TFEB, could reverse the effects of cilostazol on autophagic acti vity and lysosome activation. Importantly, cilostazol suppressed I/R injury‐induced apoptosis by decreasing the cleavage of caspase 3 and PARP. Enzyme‐linked immunosorbent assay showed that cilostazol reduced the serum levels of CTn1 and CK‐MB and decreased infract size caused by I/R injuries. Altogether this study suggested that cilostazol protects against I/R injury by regulating autophagy, lysosome, and apoptosis in a rat model of I/R injury. The protective mechanism of cilostazol was partially through increasing the transcriptional activity of TFEB.
Source: Biotechnology and Applied Biochemistry - Category: Biochemistry Authors: Tags: Original Article Source Type: research