Lycium barbarum polysaccharide protects cardiomyocytes from hypoxia/reoxygenation injury via activation of SIRT3/CypD signaling

Hailiang Wu; Yajuan Liu; Yu Hao; Dandan Hou; Ruiying Yang

doi:10.21037/atm-22-6081

Lycium barbarum polysaccharide protects cardiomyocytes from hypoxia/reoxygenation injury via activation of SIRT3/CypD signaling

Ann Transl Med. 2023 Jan 31;11(2):72. doi: 10.21037/atm-22-6081.

Authors

Hailiang Wu¹, Yajuan Liu¹, Yu Hao², Dandan Hou¹, Ruiying Yang¹

Affiliations

¹ Cadre Ward of Heart Center, General Hospital of Ningxia Medical University, Yinchuan, China.
² Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.

Abstract

Background: Myocardial ischemia-reperfusion is a common pathological feature of many heart and vascular diseases, but the molecular mechanism of this process is still unclear, and there is no effective way to protect cardiomyocytes. The aim of this study was to examine the effects and underlying molecular mechanisms of Lycium barbarum polysaccharide (LBP) on myocardial ischemia-reperfusion injury in cardiomyocytes.

Methods: The cardiomyocyte cell line H9c2 were used to establish an in vitro hypoxia/reoxygenation (H/R) model. After treatment with LBP and/or the SIRT3 inhibitor 3-TYP, cell morphology was observed under the light microscopy. The Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation, and flow cytometry was performed to assess cell apoptosis. The lysine (166)-acetylation of CypD1 was determined by co-immunoprecipitation assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the lactate dehydrogenase (LDH) level in the culture medium. Na⁺-K⁺-ATPase activity, Ca²⁺-ATPase activity, and nitric oxide (NO) levels were measured.

Results: LBP alleviated cell damage and upregulated STIR3 expression in a dose-dependent manner. Upregulated SIRT3 expression and suppressed acetylation of CypD were also observed in H/R-induced H9c2 cells treated with LBP. Indeed, LBP remarkably reversed the inhibition of proliferation and cell apoptosis in H/R-induced H9c2 cells by activating SIRT3/CypD signaling. Blockade of SIRT3 with SIRT3 inhibitor (3-TYP) inhibited the protective effect of LBP on H9c2 cells. LBP markedly alleviated the H/R-induced increase of LDH release, and the decrease of Na⁺-K⁺-ATPase activity, Ca²⁺-ATPase activity, and NO levels. Inhibition of SIRT3 restored the protective effects of LBP.

Conclusions: LPB induced deacetylation of CypD by upregulating SIRT3, thereby protecting mitochondrial function and relieving H/R-induced injury in cardiomyocytes.

Keywords: CypD; Lycium barbarum polysaccharide (LBP); Myocardial ischemia-reperfusion injury (MIRI); SIRT3; mitochondrial damage.