title: Extracellular signal-regulated kinase pathway play distinct role in acetochlor-mediated toxicity and intrinsic apoptosis in A549 cells.
abstract: Acetochlor (ACETO), a member of the chloroacetanilide family of herbicides, is widely used globally and is very frequently detected in watersheds of agricultural lands and fresh water streams. The human health consequences of environmental exposure to ACETO are unknown. This study was designed to elucidate the effect and molecular mechanisms of ACETO on human alveolar A549 cells. Established assays of cell viability and cytotoxicity were performed to detect the potential effects of ACETO on A549 cells. ACETO generated reactive oxygen species, which may have been crucial to apoptosis-mediated cytotoxicity. ACETO-treatment showed a concentration dependent up-regulation of pro-apoptotic proteins including Bax, Bak, BID and Bad, but a differential level of expression of anti-apoptotic proteins were observed, leading to the release of cytochrome c from mitochondria to the cytoplasm as well as activation of caspase-3, and cleavage of caspase-9 and PARP. ACETO also induced activation of extracellular signal-regulated kinase (ERK). Inhibition of the expression of ERK by PD98059 partially reversed ACETO-induced cytotoxicity, apoptosis and the expression of caspase-3, -9 and PARP in A549 cells. Comparative evaluation of the results indicates that the principal mechanism underlying ACETO-mediated cytotoxicity is likely to be through ERK-mediated intrinsic pathway of apoptosis.
authors.affiliation: Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 330-090, South Korea.
authors.forename: Tamanna
authors.initials: T
authors.lastname: Zerin
authors.affiliation: Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 330-090, South Korea.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
authors.affiliation: Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 330-090, South Korea. Electronic address: yongsikkim@sch.ac.kr.
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000502:physiology; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis; D014052:Toluidines / Q000633:toxicity*
chemical_list: D006540:Herbicides; D017382:Reactive Oxygen Species; D014052:Toluidines; C043377:acetochlor; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Acetochlor; Cytochrome c; Extracellular signal-regulated kinase; Pro-survival and pro-apoptotic proteins