{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:49:36Z","timestamp":1790542176749,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81300094"],"award-info":[{"award-number":["81300094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770411"],"award-info":[{"award-number":["81770411"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To explore the role of autophagic flux in the increased susceptibility of the experimental diabetic heart to ischaemia\u2010reperfusion (I\/R) injury, we established STZ\u2010induced 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\u2010induced 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\u2010dependent 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\u2010related proteins, were significantly degraded in diabetic I\/R hearts, alterations that were associated with calpain activation and could be reversed by calpain inhibition. Co\u2010overexpression 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\u2010induced injury. Calpain activation and cleavage of Atg5 and LAMP2 at least partially account for the deterioration of autophagic flux impairment.<\/jats:p>","DOI":"10.1111\/jcmm.17642","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:43:57Z","timestamp":1671767037000},"page":"232-245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Experimental diabetes exacerbates autophagic flux impairment during myocardial I\/R injury through calpain\u2010mediated cleavage of Atg5\/\n                    <scp>LAMP2<\/scp>"],"prefix":"10.1111","volume":"27","author":[{"given":"Lichun","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Shanghai General Hospital Shanghai Jiao Tong University, School of Medicine  Shanghai 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