title: GSK-3β promotes PA-induced apoptosis through changing β-arrestin 2 nucleus location in H9c2 cardiomyocytes.
abstract: Palmitic acid (PA), a type of saturated fatty acids, induces cardiovascular diseases by causing cardiomyocyte apoptosis with unclear mechanisms. Akt participates in PA-induced cardiomyocyte apoptosis. GSK-3β is a substrate of Akt, we investigated its role in PA-induced apoptosis. We reveal that PA inhibits GSK-3β phosphorylation accompanied by inactivation of Akt in H9c2 cardiomyocytes. We also reveal that inhibition the activity of GSK-3β by its inhibitor LiCl or knockdown by siRNA significantly attenuates PA-induced cardiomyocyte apoptosis, this suggesting that GSK-3β plays a pro-apoptotic role. To detect its downstream factors, we analyzed the roles of JNK, p38 MAPK and β-arrestin 2 (β-Arr2). Here, we report that GSK-3β regulate PA-induced cardiomyocyte apoptosis by affecting the distribution of β-Arr2. PA diminishes the protein level of β-Arr2 and changes its distribution from nucleus to cytoplasm. Either inhibition of β-Arr2 by its siRNA or overexpression of its protein level by transfection of β-Arr2 full-length plasmid promotes PA-induced cardiomyocyte apoptosis, which remind us to focus on the changes of its location. β-Arr2 siRNA decreased the background level of β-Arr2 in nucleus in normal H9c2 cells. Overexpression of β-Arr2 increased cytoplasm level of β-Arr2 as PA did. While LiCl, the inhibitor of GSK-3β decreased PA-induced apoptosis, accompany with increased nucleus level of β-Arr2. Then we concluded that GSK-3β is closely associated with cardiomyocyte apoptosis induced by PA, it performs its pro-apoptotic function by affecting the location of β-Arr2. LiCl inhibits PA-induced cardiomyocyte apoptosis, which might provide novel therapeutic for cardiovascular diseases induced by metabolic syndrome.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Fen
authors.initials: F
authors.lastname: Chang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yue
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People's Republic of China. jingzhao@sdu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Central South University, Changsha, 410023, People's Republic of China. delingyin@yahoo.com.|Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA. delingyin@yahoo.com.
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D000071560:beta-Arrestin 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071560:beta-Arrestin 2; D019308:Palmitic Acid; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Apoptosis; Cardiomyocyte; GSK-3β; LiCl; Palmitic acid; β-arrestin2