title: MicroRNA-145 suppresses ROS-induced Ca2+ overload of cardiomyocytes by targeting CaMKIIδ.
abstract: A change in intracellular free calcium (Ca(2+)) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca(2+) signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca(2+)-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H2O2-mediated Ca(2+) overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca(2+) overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca(2+)-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca(2+) overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.
authors.affiliation: Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Cha
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Jang
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Chang Yeon
authors.initials: CY
authors.lastname: Lee
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.forename: Hyang-Hee
authors.initials: HH
authors.lastname: Seo
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Choi
authors.forename: Woo-min
authors.initials: WM
authors.lastname: Jeon
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Hyun-Taek
authors.initials: HT
authors.lastname: Shin
authors.forename: Eunmi
authors.initials: E
authors.lastname: Choi
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000378:metabolism*; D035683:MicroRNAs / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium