Mechanism of tauroursodeoxycholic acid improving mitochondrial autophagy and alleviating oxygen-glucose deprivation myocardial cell injury by regulating TBC1D15
LIAO Weiyan
ZHAO Qian
CHEN Zeyu
XUAN Yue
XIONG Shengtao
LI Donglin
WANG Xiao
Abstract：Objective To elucidate the mechanism by which tauroursodeoxycholic acid(TUDCA)alleviates oxygen-glucose deprivation(OGD)-induced cardiomyocyte injury through specific regulation of TBC1D15 protein expression and subcellular localization to restore mitophagy function.Methods Primary cardiomyocytes were subjected to OGD and treated with TUDCA at low(20 μmol/L),medium(40 μmol/L),or high(80 μmol/L)doses.TBC1D15 subcellular localization and expression were assessed by immunofluorescence.Cell apoptosis/necrosis was evaluated using YO-PRO-1/PI double staining.Lysosome staining is used to detect lysosome function.Autophagy dual-labeling adenovirus HBAD-mcherry-EGFP-LC3 is used to detect the efficiency of autophagy flow.Western blot was performed to analyze autophagy-related proteins(Beclin-1,LC3-Ⅱ/Ⅰ,p62)and the anti-apoptotic protein Bcl-2.Results Compared with the normal control group,the model group showed a significant decrease in TBC1D15 expression and disordered distribution.After TUDCA intervention,the expression of TBC1D15 was restored in a dose-dependent manner.In the high-dose group,the fluorescence intensity was close to that of the normal control group,and the localization at the cell membrane was significantly enhanced.Regarding autophagy-related indicators,the medium-and high-dose TUDCA groups significantly promoted autophagy activation,which was manifested as an increase in the LC3-Ⅱ/Ⅰ ratio,accelerated degradation of p62,and increased expression of Beclin-1.The results of cell apoptosis/necrosis detection showed that cell apoptosis/necrosis was significantly increased in the model group,while it was significantly alleviated after TUDCA intervention.Meanwhile,the expression of the anti-apoptotic protein Bcl-2 was up-regulated,and this ameliorative effect was most significant in the high-dose group.Conclusion TUDCA restores TBC1D15 membrane localization in a dose-dependent manner,subsequently activating the mitophagy pathway,and ultimately synergistically inhibits apoptosis/necrosis.
Keywords：tauroursodeoxycholic acidmitochondrial autophagyTBC1D15oxygen-glucose depriva-tioncardiomyocyte injury
Publication Date：2026-01-25
Online Publishing Date：2026-01-28(First online date of this platform, not the publication date of the document)
Pages：10( 220-229 )