Sulfiredoxin-1 protects against simulated ischaemia/reperfusion injury in cardiomyocyte by inhibiting PI3K/AKT-regulated mitochondrial apoptotic pathways | Zendy

Jiankai Zhang | Zendy; Zhangyou He | Zendy; Jinhua Guo | Zendy; Zhe Li | Zendy; Xiaohong Wang | Zendy; Chun Yang | Zendy; Xiaojun Cui | Zendy

Open Access

Sulfiredoxin-1 protects against simulated ischaemia/reperfusion injury in cardiomyocyte by inhibiting PI3K/AKT-regulated mitochondrial apoptotic pathways

Author(s) -

Jiankai Zhang,

Zhangyou He,

Jinhua Guo,

Zhe Li,

Xiaohong Wang,

Chun Yang,

Xiaojun Cui

Publication year - 2016

Publication title -

bioscience reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.938

H-Index - 77

eISSN - 1573-4935

pISSN - 0144-8463

DOI - 10.1042/bsr20160076

Subject(s) - pi3k/akt/mtor pathway , protein kinase b , apoptosis , cytochrome c , ly294002 , reactive oxygen species , microbiology and biotechnology , neuroprotection , viability assay , lactate dehydrogenase , reperfusion injury , biology , caspase 3 , oxidative stress , chemistry , pharmacology , biochemistry , programmed cell death , ischemia , medicine , enzyme

Reactive oxygen species (ROS)-triggered cardiac cell injury is recognized as the major contributor for the pathogenesis progression of ischaemic cardiovascular diseases. Sulfiredoxin-1 (Srx-1) is an endogenous antioxidant and exerts the crucial neuroprotective effects in cerebral ischaemia. However, its function and the underlying mechanism in ischaemic heart diseases remain poorly defined. Here, a dramatical decrease in Srx-1 was validated in H9c2 cardiomyocytes upon simulated ischaemia-reperfusion (SI/R) injury. Moreover, Srx-1 protected H9c2 cells from SI/R-injured injury as the evidences that Srx-1 up-regulation attenuated the inhibitory effects on cell viability, lactate dehydrogenase (LDH) and cell apoptosis upon SI/R treatment. Knockdown of Srx-1 accelerated cell injury upon SI/R. Mechanism assay corroborated that SI/R treatment noticeably aggravated the loss of mitochondrial membrane potential (Δψm), which was remarkably abated in Ad-Srx-1 groups. Importantly, Srx-1 elevation substantially reduced cytochrome c release, the activity of caspase-9 and caspase-3, accompany with the subsequent decrease in the cleavage of poly (ADP ribose) polymerase (PARP). Concomitantly, overexpression of Srx-1 also decreased the expression of pro-apoptosis protein Bax and increased anti-apoptotic Bcl-2 expression. Further analysis substantiated that Srx-1 treatment remarkably induced the activation of PI3K/AKT signalling. Preconditioning with LY294002 dramatically decreased Srx-1-enhanced cell resistance to SI/R injury. Importantly, LY294002 mitigated the inhibitory effects of Srx-1 on Δψm loss, cytochrome c release, caspase-9/3 activity, and the expression of Bcl-2 family. Together, these results suggested that Srx-1 might protect cardiomyocyte injury upon SI/R by suppressing PI3K/AKT-mediated mitochondria dependent apoptosis, revealing a promising therapeutic agent against ischaemic cardiovascular diseases.

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