| First Author | Guan L | Year | 2023 |
| Journal | J Cell Mol Med | Volume | 27 |
| Issue | 2 | Pages | 232-245 |
| PubMed ID | 36562207 | Mgi Jnum | J:344542 |
| Mgi Id | MGI:7430312 | Doi | 10.1111/jcmm.17642 |
| Citation | Guan L, et al. (2023) Experimental diabetes exacerbates autophagic flux impairment during myocardial I/R injury through calpain-mediated cleavage of Atg5/LAMP2. J Cell Mol Med 27(2):232-245 |
| abstractText | To explore the role of autophagic flux in the increased susceptibility of the experimental diabetic heart to ischaemia-reperfusion (I/R) injury, we established STZ-induced diabetic mice and performed I/R. In vitro, neonatal mouse cardiomyocytes were subjected to high glucose and hypoxia/reoxygenation challenge to mimic diabetic I/R injury. We found that experimental diabetes aggravated I/R-induced injury than compared with nondiabetic mice. Autophagic flux was impaired in I/R hearts, and the impairment was exacerbated in diabetic mice subjected to I/R with defective autophagosome formation and clearance. Calpains, calcium-dependent thiol proteases, were upregulated and highly activated after I/R of diabetes, while calpain inhibition attenuated cardiac function and cell death and partially restored autophagic flux. The expression levels of Atg5 and LAMP2, two crucial autophagy-related proteins, were significantly degraded in diabetic I/R hearts, alterations that were associated with calpain activation and could be reversed by calpain inhibition. Co-overexpression of Atg5 and LAMP2 reduced myocardial injury and normalized autophagic flux. In conclusion, experimental diabetes exacerbates autophagic flux impairment of cardiomyocytes under I/R stress, resulting in worse I/R-induced injury. Calpain activation and cleavage of Atg5 and LAMP2 at least partially account for the deterioration of autophagic flux impairment. |
