Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.

Abstract

The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.

• Authors: Hua-Li Chen, Yan Liu, Wei Jiang, Xiao-Xiao Wang, Guo-Lin Yuan, Yi-Lin Zhao, Chao Yu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 822 Pg. 13-24 (Mar 05 2018) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 29337195 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Neuropeptides
• Reactive Oxygen Species
• Secretogranin II
• secretoneurin
• Catalase
• Superoxide Dismutase
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Catalase (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Hypertrophy (drug therapy, metabolism, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Neuropeptides (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Secretogranin II (pharmacology, therapeutic use)
• Superoxide Dismutase (metabolism)