title: Overproduction of reactive oxygen species and activation of MAPKs are involved in apoptosis induced by PM2.5 in rat cardiac H9c2 cells.
abstract: Epidemiological studies show a positive correlation between the air levels of fine particulate matter (PM2.5) and cardiovascular disorders, but how PM2.5 affects cardiomyocytes has not been studied in great deal. The aim of the present study was to obtain an insight into the links among intracellular levels of reactive oxygen species (ROS), apoptosis and mitogen-activated protein kinases (MAPKs) in rat cardiac H9c2 cells exposed to PM2.5. H9c2 cells were incubated with PM2.5 at 100-800 µg ml(-1) to evaluate the effects of PM2.5 on cell viability, cell apoptosis, intracellular levels of ROS and expression of apoptosis-related proteins as well as activation of MAPKs. PM2.5 decreased cell viability, increased the cell apoptosis rate and intracellular ROS production in a concentration-dependent manner. PM2.5 decreased the Bcl-2/Bax ratio and increased cleaved caspase-3 levels. A Western blots study showed up-regulation of phosphorylated MAPKs including extracellular signal-regulated protein kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK in the PM2.5-treated cells. The p38 MAPK inhibitor SB239063 attenuated whereas the ERKs inhibitor PD98059 augmented the effects of PM2.5 on apoptosis and the expression of related proteins. In conclusion, PM2.5 decreases cell viability and increases apoptosis by enhancing intracellular ROS production and activating the MAPKs signaling pathway in H9c2 cells. The MAPKs signaling pathway could be a new promising target for clinical therapeutic strategies against PM2.5-induced cardiac injury.
authors.affiliation: The First Clinical Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: The First Clinical Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Qin
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Ruizan
authors.initials: R
authors.lastname: Shi
authors.affiliation: The First Clinical Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: The First Clinical Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Guangzhao
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: The First Clinical Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: H9c2 cells; apoptosis; fine particulate matter; mitogen-activated protein kinases; reactive oxygen species