title: Suppression of rat Frizzled-2 attenuates hypoxia/reoxygenation-induced Ca2+ accumulation in rat H9c2 cells.
abstract: Growing evidence suggests that Ca(2+) overload is one of the major contributors of myocardial ischemia/reperfusion-induced injury. Since Frizzled-2 receptor, a seven transmembrane protein, transduces downstream signaling by specialized binding of Wnt5a to increase intracellular Ca(2+) release, this work aimed to investigate the effect of Frizzled-2 on Ca(2+) accumulation in H9c2 cells, which were subjected to hypoxia/reoxygenation to mimic myocardial ischemia/reperfusion. After exposing H9c2 cells to hypoxia/reoxygenation, we observed higher expression of Frizzled-2 and Wnt5a as compared to control group cells. Hypoxia/reoxygenation-induced intracellular Ca(2+) accumulation approached that of cells transfected with frizzled-2 plasmid. In cells treated with RNAi specifically designed against frizzled-2, intracellular Ca(2+) in both hypoxia/reoxygenation-treated cells and plasmid-treated cells were decreased. Rats that underwent ischemia/reperfusion injury exhibited increased intracellular Ca(2+) with high expression levels of Frizzled-2 and Wnt5a as compared to the sham group. Our data indicates that upon binding to Wnt5a, increased Frizzled-2 expression after hypoxia/reoxygenation treatment activated intracellular calcium release in H9c2 cells. Our findings provide a new perspective in understanding calcium overload in myocardial ischemia/reperfusion.
authors.affiliation: Department of Cardiology, Southern Medical University/Zhujiang Hospital, China.
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Zhou
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Chen
authors.forename: Pei-yuan
authors.initials: PY
authors.lastname: Hao
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002999:Clone Cells; D051157:Frizzled Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D051157:Frizzled Receptors; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; C078604:Fzd2 protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010100:Oxygen; D002118:Calcium