title: Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion.
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.
authors.affiliation: 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.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Kadowaki
authors.affiliation: 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.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shishido
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 iidanihi, Yamagata 990-9585, Japan. toshikisasaki@yahoo.co.jp.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: 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.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugai
authors.affiliation: 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.
authors.forename: Taro
authors.initials: T
authors.lastname: Narumi
authors.affiliation: 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.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Honda
authors.affiliation: 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.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Otaki
authors.affiliation: 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.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kinoshita
authors.affiliation: 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.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: 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.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Takanori
authors.initials: T
authors.lastname: Arimoto
authors.affiliation: 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.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: 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.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. ishigami@timig.or.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishigami
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan. takeishi@fmu.ac.jp.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.affiliation: 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.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; C513324:Rgn protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: GSK-3β; SMP30; cardiomyocyte; ischemia reperfusion