Hyperglycemia-induced SIRT3 inhibition contributes to diabetic cardiomyopathy by impairing Cav-3-mediated mitophagy.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Hyperglycemia-induced SIRT3 inhibition contributes to diabetic cardiomyopathy by impairing Cav-3-mediated mitophagy.
Συγγραφείς: Jin Z; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Ji Y; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Su W; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Zhou L; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Gao L; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Wen X; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Tang H; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Xia ZY; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China., Lei S; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: leishaoqing@163.com.
Πηγή: Biochemical pharmacology [Biochem Pharmacol] 2026 Jun; Vol. 248, pp. 117835. Date of Electronic Publication: 2026 Feb 20.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE
Imprint Name(s): Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
Ιατρικοί όροι (MeSH): Sirtuin 3*/antagonists & inhibitors , Sirtuin 3*/metabolism , Sirtuin 3*/genetics , Diabetic Cardiomyopathies*/metabolism , Diabetic Cardiomyopathies*/pathology , Mitophagy*/physiology , Mitophagy*/drug effects , Caveolin 3*/metabolism , Caveolin 3*/genetics , Caveolin 3*/antagonists & inhibitors , Hyperglycemia*/metabolism , Hyperglycemia*/pathology, Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/pathology ; Diabetes Mellitus, Experimental/metabolism ; Animals ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Male ; Rats ; Cell Line
Περίληψη: Diabetic cardiomyopathy (DCM) is a major cause of mortality in diabetic patients, with impaired mitophagy contributing its pathogenesis. Sirtuin 3 (SIRT3) and caveolin-3 (Cav-3) are protective proteins involved in mitophagy, although their precise mechanisms remain unclear. This study investigated the interplay between SIRT3, Cav-3, and mitophagy in DCM. We found that the diabetic C57BL/6 mice exhibited impaired cardiac structure and function, accompanied by reduced mitophagy and decreased expression of SIRT3 and Cav-3. Cav-3 KO mice with diabetes showed further worsened cardiac dysfunction and mitophagy impairment without further affecting SIRT3 expression. In cultured H9C2 cardiomyocytes, both SIRT3 siRNA and Cav-3 siRNA exacerbated high glucose (HG)-induced cardiomyocyte damage and reduced mitophagy occurrence. Interestingly, SIRT3 siRNA significantly decreased Cav-3 expression, but vice not. Additionally, Cav-3 overexpression rescued HG-induced cardiomyocyte injury and mitophagy impairment without affecting SIRT3 expression. Collectively, our findings suggest that hyperglycemia-induced SIRT3 suppression contributes to DCM by impairing Cav-3-mediated mitophagy.
(Copyright © 2026. Published by Elsevier Inc.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Cav-3; Diabetes; Diabetic cardiomyopathy; Mitophagy; SIRT3
Substance Nomenclature: EC 3.5.1.- (Sirtuin 3)
0 (Caveolin 3)
0 (Sirt3 protein, mouse)
0 (Cav3 protein, mouse)
Entry Date(s): Date Created: 20260222 Date Completed: 20260708 Latest Revision: 20260708
Update Code: 20260708
DOI: 10.1016/j.bcp.2026.117835
PMID: 41724275
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1873-2968
DOI:10.1016/j.bcp.2026.117835