Life Sciences. 207():492–498, AUG 2018
DOI: 10.1016/j.lfs.2018.06.029
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PMID: 29964055
Issn Print: 0024-3205
Publication Date: 2018/08/01
C1qTNF-related protein 1 attenuates doxorubicin-induced cardiac injury via activation of AKT
Hongrui Chen;Lu Gao;Zhen Huang;Yuan Liu;Sen Guo;Junhui Xing;Zhe Meng;Cui Liang;Yapeng Li;Rui Yao;Ling Li;Yanzhou Zhang;Heping Gu;Yuzhou Liu;
+ Author Information
Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China
Abstract
The clinical use of doxorubicin (Dox) is limited due to a degenerative irreversible cardiac toxicity, but the precise mechanisms that contribute to this pathological response are not understood. C1q/TNF-related protein 1 (CTRP1), which is a conserved protein of the C1q family, has notable metabolic and cardiovascular functions. However, whether CTRP1 can attenuate Dox-induced cardiac injury remains unclear. Our study aimed to investigate the effect of CTRP1 on Dox-induced cardiotoxicity and assessed the mechanisms of this effect.We manipulated CTRP1 expression in the heart using in vivo gene delivery system. Two weeks after gene delivery, the mice received a single intraperitoneal injection of Dox (20mg/kg) to induce cardiac injury.Cardiac CTRP1 protein levels were decreased in DOX-treated mice. CTRP1 overexpression reduced plasma cardiac troponin I, restored cardiac function and attenuated cardiomyocyte apoptosis in Dox-treated mice. CTRP1 also improved cell viability and reduced lactate dehydrogenase release in vitro. Dox resulted in the decreased the protein kinase B (PKB/AKT) phosphorylation, which were restored by CTRP1 overexpression. AKT inhibition offset the inhibitory effects of CTRP1 on myocyte apoptosis in vitro. CTRP1 lost its protection against Dox-induced cardiac injury in mice with AKT deficiency. Furthermore, infusion of recombinant CTRP1 protein could reverse pre-established injury in heart induced by Dox treatment.In conclusion, CTRP1 protected against Dox-induced cardiotoxicity via activation of AKT. CTRP1 has the therapeutic potential to treat Dox-induced cardiotoxicity.
