Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion
AbstractEarly 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. View Full-Text
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Kadowaki, S.; Shishido, T.; Sasaki, T.; Sugai, T.; Narumi, T.; Honda, Y.; Otaki, Y.; Kinoshita, D.; Takahashi, T.; Nishiyama, S.; Takahashi, H.; Arimoto, T.; Miyamoto, T.; Watanabe, T.; Ishigami, A.; Takeishi, Y.; Kubota, I. Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion. Int. J. Mol. Sci. 2016, 17, 542.
Kadowaki S, Shishido T, Sasaki T, Sugai T, Narumi T, Honda Y, Otaki Y, Kinoshita D, Takahashi T, Nishiyama S, Takahashi H, Arimoto T, Miyamoto T, Watanabe T, Ishigami A, Takeishi Y, Kubota I. Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion. International Journal of Molecular Sciences. 2016; 17(4):542.Chicago/Turabian Style
Kadowaki, Shinpei; Shishido, Tetsuro; Sasaki, Toshiki; Sugai, Takayuki; Narumi, Taro; Honda, Yuki; Otaki, Yoichiro; Kinoshita, Daisuke; Takahashi, Tetsuya; Nishiyama, Satoshi; Takahashi, Hiroki; Arimoto, Takanori; Miyamoto, Takuya; Watanabe, Tetsu; Ishigami, Akihiko; Takeishi, Yasuchika; Kubota, Isao. 2016. "Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion." Int. J. Mol. Sci. 17, no. 4: 542.
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