title: Palmitate promotes autophagy and apoptosis through ROS-dependent JNK and p38 MAPK.
abstract: Palmitate (PA), one of the most prevalent saturated fatty acids, causes myocardial dysfunction. However, the mechanisms by which PA induces cell apoptosis and autophagy remain to be elucidated. We showed that autophagy was induced in an mTORC1-dependent way and played a protective role against PA-induced apoptosis, which was verified by pretreatment with 3-methyladenine (3MA) and rapamycin. However, p62 began to accumulate after 18 h treatment with PA, suggesting prolonged exposure to PA lead to an impairment of autophagic flux. PA enhanced ROS production as well as activated p38-mitogen-activated protein kinase (p38 MAPK) and c-jun NH2 terminal kinases (JNKs). The antioxidant N-Acety-l-Cysteine (NAC) was found to attenuate the JNK and p38 MAPK activation with a concomitant reduction of PA-induced autophagy and apoptosis. Furthermore, both JNK and p38 MAPK inhibitors were shown to directly abrogate caspase 7 cleavage as well as the conversion of LC3BI to LC3BII. Thus, we demonstrate that PA stimulates autophagy and apoptosis via ROS-dependent JNK and p38 MAPK pathways.
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Chang
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fu
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Shangli
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China. Electronic address: jingzhao@sdu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. Electronic address: yin@etsu.edu.
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D010168:Palmitates / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D010168:Palmitates; D017382:Reactive Oxygen Species; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Autophagy; JNK; Palmitate; ROS; p38 MAPK