title: Inhibition of aroclor 1254-induced depletion of stored calcium prevents the cell death in catecholaminergic cells.
abstract: The relationship between depleting effects of polychlorinated biphenyls (PCBs) on the intracellular calcium store and PCBs-induced cell death in dopaminergic cells has not been fully evaluated. Here, we evaluated the effects of inhibitors of the release of ER-stored calcium on the cytotoxicities induced by 10 microg/ml of Aroclor 1254 (A1254; polychlorinated biphenyl mixture) in a catecholaminergic cell-line, CATH.a cells. Exposure to A1254 produced an elevation in free calcium ([Ca2+]i) in the presence or absence of extracellular calcium and decreased in cell viability. From our results, we deduced that the A1254-induced elevation of [Ca2+]i resulted from the depletion of ER-stored calcium. The [Ca2+)]i elevation was dramatically inhibited by an inositol 1,4,5-triphosphate receptor (IP3R) antagonist, and slightly inhibited by a ryanodine receptor (RyR) blocker. IP3R blockers conferred significant protection against A1254-induced cell death, as did RyR blockers, but calcium chelators or NMDA blockers did not. However, none of these reagents inhibited the depletion of intracellular dopamine by A1254 indicating that the mechanism of PCB-induced dopamine depletion may be independent of calcium alterations. Taken together, these data suggest that agents inhibiting the receptor-mediated depletion of stored calcium can prevent the A1254-induced cell death, but not modulate the A1254-induced intracellular dopamine depletion in CATH.a cells.
authors.affiliation: Department of Pharmacology and Toxicology, College of Medicine, Inha University, Incheon 402-751, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Park
authors.forename: Woo-Yong
authors.initials: WY
authors.lastname: Oh
authors.forename: Hwa-Kyung
authors.initials: HK
authors.lastname: Lim
authors.forename: So-Young
authors.initials: SY
authors.lastname: Wang
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Choi
authors.forename: Joo-il
authors.initials: JI
authors.lastname: Kim
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Jung
authors.forename: Chang Kook
authors.initials: CK
authors.lastname: Suh
authors.forename: Dong Sup
authors.initials: DS
authors.lastname: Kim
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels; D002395:Catecholamines / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D020111:Chlorodiphenyl (54% Chlorine) / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D047028:Macrocyclic Compounds; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; C108644:xestospongin A; D020111:Chlorodiphenyl (54% Chlorine); D019284:Thapsigargin; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D002118:Calcium; D004298:Dopamine