title: Oxidative stress and Ca(2+) signals involved on cadmium-induced apoptosis in rat hepatocyte.
abstract: Cadmium (Cd) is an important industrial and environmental pollutant. In animals, the liver is the major target organ of Cd toxicity. In this study, rat hepatocytes were treated with 2.5∼10 μM Cd for various durations. Studies on nuclear morphology, chromatin condensation, and apoptotic cells demonstrate that Cd concentrations ranging within 2.5∼10 μM induced apoptosis. The early-stage marker of apoptosis, i.e., decreased mitochondrial membrane potential, was observed as early as 1.5 h at 5 μM Cd. Significant (P < 0.01) reactive oxygen species (ROS) production at 5 μM Cd and 0.75 h occurred prior to the decrease of the mitochondrial membrane potential, suggesting the involvement of ROS in mitochondrial membrane damage. Glutathione (GSH) level significantly decreased after cell treatment with 5 and 10 μM Cd after 12 h (P < 0.01). Meanwhile, the intracellular free Ca(2+) concentration ([Ca(2+)] i ) of Cd-exposed cells significantly increased (P < 0.01) at 1.5 h, and pretreatment with the calcium chelator Bapta-AM partially blocked Cd-induced apoptosis. This finding indicated that the elevation of [Ca(2+)] i may play an important role in apoptosis. Overall, these results showed that oxidative stress and Ca(2+) signaling were critical mediators of the Cd-induced apoptosis of rat hepatocytes.
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, No. 70 Tianjin Road, Luoyang, 471003, People's Republic of China, wangjicang@126.com.
authors.forename: Jicang
authors.initials: J
authors.lastname: Wang
authors.forename: Huali
authors.initials: H
authors.lastname: Zhu
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Zongping
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D020013:Calcium Signaling / Q000187:drug effects*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002104:Cadmium