title: Extracellular-superoxide dismutase expression in COS7 cells exposed to cadmium chloride.
abstract: Cadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactive oxygen species (ROS) and induces cytotoxicity. Extracellular-superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the cells from damaging effects of ROS; however, the effect of Cd on the expression of EC-SOD in COS7 cells remains unclear. In this study, exposure to cadmium chloride (CdCl₂) enhanced intracellular ROS generation and induced COS7 cell death. Moreover, exposure to Cd decreased the expression of EC-SOD at mRNA and protein levels, but not of other SOD isozymes, copper-and zinc-containing SOD and manganese-containing SOD. The reduction of EC-SOD and cell viability was partially attenuated by pretreatment with an antioxidant, N-acetylcysteine. Further, we determined the involvement of p38-mitogen-activated protein kinase (p38-MAPK) in the reduction of EC-SOD. From these observations, p38-MAPK signaling cascades activated by ROS play a pivotal role in the reduction of EC-SOD, and it is concluded that the reduction of EC-SOD leads to a decrease in the resistance to oxidative stress of Cd-exposed COS7 cells.
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Japan.
authors: Aya
authors: A
authors: Obara
authors: Tetsuro
authors: T
authors: Kamiya
authors: Misato
authors: M
authors: Izumi
authors: Hirokazu
authors: H
authors: Hara
authors: Harutaka
authors: H
authors: Yamada
authors: Tetsuo
authors: T
authors: Adachi
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D019256:Cadmium Chloride / Q000633:toxicity*; D016923:Cell Death; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D005110:Extracellular Space / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D019256:Cadmium Chloride