Academic Journal
Hyperglycemia-induced SIRT3 inhibition contributes to diabetic cardiomyopathy by impairing Cav-3-mediated mitophagy.
| Τίτλος: | Hyperglycemia-induced SIRT3 inhibition contributes to diabetic cardiomyopathy by impairing Cav-3-mediated mitophagy. |
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| 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 |
| ISSN: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2026.117835 |