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Int J Mol Sci. 2016 Apr 11;17(4):542. doi: 10.3390/ijms17040542.

Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion.

Author information

1
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. s-kadowaki@med.id.yamagata-u.ac.jp.
2
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. tshishid@med.id.yamagata-u.ac.jp.
3
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. toshikisasaki@yahoo.co.jp.
4
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. t-sugai@med.id.yamagata-u.ac.jp.
5
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. t-narumi@med.id.yamagata-u.ac.jp.
6
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. y-honda@med.id.yamagata-u.ac.jp.
7
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. y-otaki@med.id.yamagata-u.ac.jp.
8
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. d-kinoshita@med.id.yamagata-u.ac.jp.
9
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. t.tetsuya@med.id.yamagata-u.ac.jp.
10
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. mnisiyam@med.id.yamagata-u.ac.jp.
11
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. hitakaha@med.id.yamagata-u.ac.jp.
12
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. t-arimoto@med.id.yamagata-u.ac.jp.
13
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. tamiyamo@med.id.yamagata-u.ac.jp.
14
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. tewatana@med.id.yamagata-u.ac.jp.
15
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. ishigami@timig.or.jp.
16
Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan. takeishi@fmu.ac.jp.
17
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. ikubota@med.id.yamagata-u.ac.jp.

Abstract

Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R) causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30), whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion in wild-type (WT) and SMP30 knockout (KO) mice. After I/R, cardiomyocyte apoptosis and the ratio of infarct area/area at risk were higher, left ventricular fractional shortening was lower, and reactive oxygen species (ROS) generation was enhanced in SMP30 KO mice. Moreover, the previously increased phosphorylation of GSK-3β and Akt was lower in SMP30 KO mice than in WT mice. In cardiomyocytes, silencing of SMP30 expression attenuated Akt and GSK-3β phosphorylation, and increased Bax to Bcl-2 ratio and cardiomyocyte apoptosis induced by hydrogen peroxide. These results suggested that SMP30 deficiency augments myocardial I/R injury through ROS generation and attenuation of Akt activation.

KEYWORDS:

GSK-3β; SMP30; cardiomyocyte; ischemia reperfusion

PMID:
27077846
PMCID:
PMC4848998
DOI:
10.3390/ijms17040542
[Indexed for MEDLINE]
Free PMC Article

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