SRPIN340 protects heart muscle from oxidative damage via SRPK1/2 inhibition-mediated AKT activation

Jian Huang; Yaqun Zhou; Xiaoyu Xue; Liudan Jiang; Jimin Du; Yingyu Cui; Hong Zhao

doi:10.1016/j.bbrc.2019.01.054

SRPIN340 protects heart muscle from oxidative damage via SRPK1/2 inhibition-mediated AKT activation

Biochem Biophys Res Commun. 2019 Feb 26;510(1):97-103. doi: 10.1016/j.bbrc.2019.01.054. Epub 2019 Jan 17.

Authors

Jian Huang¹, Yaqun Zhou², Xiaoyu Xue², Liudan Jiang¹, Jimin Du¹, Yingyu Cui³, Hong Zhao⁴

Affiliations

¹ Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
² Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China.
³ Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
⁴ Department of Pediatrics, Tongji Hospital, Tongji University, Shanghai 200120, China. Electronic address: zhaohong_tj@163.com.

PMID: 30661787
DOI: 10.1016/j.bbrc.2019.01.054

Abstract

SRPIN340, a selective serine-arginine protein kinase 1/2 (SRPK1/2) inhibitor, has been shown to have antiviral and anti-angiogenesis effects. However, its role in the heart is unknown. The present study explored the role of SRPIN340 in myocardial protection and the related mechanisms. During challenge with H₂O₂, cardiomyocytes (CMs) pretreated with SRPIN340 showed strikingly more injury tolerance, which was manifested as reduced lactate dehydrogenase (LDH) release and lower apoptotic index. Further research showed that SRPIN340 activated AKT under basal conditions, and AKT inhibition abolished the protective effects of SRPIN340 treatment during H₂O₂ stress. The protective effect of SRPIN340 was also demonstrated in perfused rat hearts subjected to ischemia/reperfusion (I/R). Collectively, our results reveal the beneficial effects of SRPIN340 against H₂O₂-induced oxidative damage in CMs and I/R-induced injury in a Langendorff heart model, supporting a potential application of SRPIN340 in the clinically relevant context of reperfusion. The effectiveness of SRPIN340 may be attributed to AKT signal activation.

Keywords: AKT; Apoptosis; Cardiomyocyte; Ischemia-reperfusion; Oxidative injury; SRPIN340.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Heart / drug effects
Hydrogen Peroxide / pharmacology
Myocardial Reperfusion Injury / prevention & control
Myocardium*
Niacinamide / analogs & derivatives*
Niacinamide / pharmacology
Niacinamide / therapeutic use
Oxidative Stress / drug effects*
Piperidines / pharmacology*
Piperidines / therapeutic use
Protective Agents / pharmacology
Protective Agents / therapeutic use
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / metabolism
Rats
Signal Transduction

Substances

Piperidines
Protective Agents
SRPIN340
Niacinamide
Hydrogen Peroxide
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt