title: Na(+)-Ca(2+) exchanger targeting miR-132 prevents apoptosis of cardiomyocytes under hypoxic condition by suppressing Ca(2+) overload.
abstract: During ischemia-reperfusion (IR) injury of the heart, Ca(2+) overload occurs, leading to cardiomyocyte dysfunction and eventual cell death by apoptosis. Since preventing Ca(2+) overload during IR injury has been reported to protect cardiomyocytes, interrupting Ca(2+) signaling cascades leading to Ca(2+) overload may exert protective effect on cardiomyocytes under hypoxic condition. One of the key regulators of the intracellular Ca(2+) level during IR injury is Na(+)-Ca(2+) exchanger 1 (NCX1), whose down-regulation during IR injury conferred protection of heart. In the present study, we examined whether down-regulation of NCX1 using exogenous microRNA ameliorates apoptosis of cardiomyocytes under hypoxic condition. Here, we identified miR-132 as a novel microRNA targeting the NCX1, whose expression increased during hypoxia. Delivery of miR-132 suppressed the increase of intracellular Ca(2+) in cardiomyocytes under hypoxia, and the expressions of apoptotic molecules, such as Bax, cytochrome C, and caspase 3, and the number of apoptotic cells were also decreased by exogenous miR-132 treatment. These results suggest the potential of miR-132 as an effective therapeutic agent against IR damage to heart by preventing Ca(2+) overload during hypoxic condition and warrant further studies to validate its anti-apoptotic effect in vivo.
authors.affiliation: Department of Medicine, The Graduate School, Yonsei University, Seoul 120-752, Republic of Korea; Department of Thoracic & Cardiovascular Surgery, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do 220-710, Republic of Korea.
authors.forename: Soonchang
authors.initials: S
authors.lastname: Hong
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Republic of Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Republic of Korea.
authors.forename: Hyang-Hee
authors.initials: HH
authors.lastname: Seo
authors.affiliation: Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Chang Yeon
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Yoo
authors.affiliation: Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City 404-834, Republic of Korea.
authors.forename: Sung-Man
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City 404-834, Republic of Korea; Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Republic of Korea.
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City 404-834, Republic of Korea; Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Republic of Korea. Electronic address: kchwang@cku.ac.kr.
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
authors.affiliation: Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City 404-834, Republic of Korea; Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Republic of Korea. Electronic address: ehchoi@ish.or.kr.
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: C548821:MIRN132 microRNA, rat; D035683:MicroRNAs; D019831:Sodium-Calcium Exchanger; D002118:Calcium
keywords: Apoptosis; Ca(2+) overload; Cardiomyocyte; Hypoxia; NCX; miR-132