Trans sodium crocetinate alleviates ischemia/reperfusion-induced myocardial oxidative stress and apoptosis via the SIRT3/FOXO3a/SOD2 signaling pathway.

Abstract:

:Trans sodium crocetinate (TSC) has been reported to exert a protective effect against cerebral ischemia/reperfusion (I/R) injury. However, whether TSC protects against myocardial ischemia/reperfusion (MI/R) injury remains unknown. Herein, we found that TSC treatment reduced myocardial infract size and elevated serum LDH and CK activities of MI/R rats. TSC administration attenuated oxidative stress in MI/R rats and H9C2 cells exposed to oxygen glucose deprivation/reperfusion (OGD/R). TSC administration relieved I/R-induced myocardial apoptosis in vivo and in vitro, as evidenced by reduced number of TUNEL positive cells, accompanying with marked decreases in caspase-3 activity and Bax protein level and an increase in Bcl-2 protein level. TSC treatment markedly increased SIRT3 activity and SIRT3 and SOD2 protein levels, and could also diminished the phosphorylation of FOXO3a protein. Additionally, TSC treatment attenuated the acetylation of FOXO3a and SOD2 protein. But, these effects were obviously blocked by SIRT3 knockdown. Besides, SIRT3 knockdown blocked the cardioprotective effect of TSC on OGD/R-induced oxidative stress, apoptosis and mitochondrial dysfunction in vitro. In summary, TSC alleviates I/R-induced myocardial oxidative stress and apoptosis via the SIRT3/FOXO3a/SOD2 signaling pathway. Our study suggests that TSC may become a novel drug for the treatment of MI/R injury.

journal_name

Int Immunopharmacol

authors

Chang G,Chen Y,Zhang H,Zhou W

doi

10.1016/j.intimp.2019.03.056

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

361-371

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)31416-4

journal_volume

71

pub_type

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