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Protective effects of kenpaullone on cardiomyocytes following H2O2-induced oxidative stress are attributed to inhibition of connexin 43 degradation by SGSM3

 Hyun-Chel Joo  ;  Jung-Won Choi  ;  Hanbyeol Moon  ;  Chang Youn Lee  ;  Kyung-Jong Yoo  ;  Sang Woo Kim  ;  Ki-Chul Hwang 
 Biochemical and Biophysical Research Communications, Vol.499(2) : 368-373, 2018 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Cardiomyocytes ; Connexin 43 ; Gap junction ; Oxidative stress ; SGSM3
A previous study showed that small G protein signaling modulator 3 (SGSM3) was highly correlated with Cx43 in heart functions and that high levels of SGSM3 may induce Cx43 turnover through lysosomal degradation in infarcted rat hearts. Here, we investigated the protective effects of kenpaullone on cardiomyocytes following H2O2-induced oxidative stress mediated by the interaction of SGSM3 with Cx43. We found that the gap junction protein Cx43 was significantly down-regulated in an H2O2 concentration-dependent manner, whereas expression of SGSM3 was up-regulated upon H2O2 exposure in H9c2 cells. The effect of kenpaullone pretreatment on H2O2-induced cytotoxicity was evaluated in H9c2 cells. H2O2 markedly increased the release of lactate dehydrogenase (LDH), while kenpaullone pretreatment suppressed LDH release in H9c2 cells. Moreover, kenpaullone pretreatment significantly reduced ROS fluorescence intensity and significantly down-regulated the level of apoptosis-activating genes (cleaved caspase-3, cleaved caspase-9 and cytochrome C), autophagy markers (LC3A/B), and the Cx43-interacting partner SGSM3. These results suggest that kenpaullone plays a role in protecting cardiomyocytes from oxidative stress and that the turnover of Cx43 through SGSM3-induced lysosomal degradation underlies the anti-apoptotic effect of kenpaullone.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
유경종(Yoo, Kyung Jong) ORCID logo https://orcid.org/0000-0002-9858-140X
주현철(Joo, Hyun Chel) ORCID logo https://orcid.org/0000-0002-6842-2942
황기철(Hwang, Ki Chul)
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