title: Characterization of cocaine-elicited cell vacuolation: the involvement of calcium/calmodulin in organelle deregulation.
abstract: The sizes of organelles are tightly regulated in the cells. However, little is known on how cells maintain the homeostasis of these intracellular compartments. Using cocaine as a model compound, we have characterized the mechanism of deregulated vacuolation in cultured rat liver epithelial Clone 9 cells. The vacuoles were observed as early as 10 min following cocaine treatment. Removal of cocaine led to vacuole degeneration, indicating vacuolation is a reversible process. The vacuoles could devour intracellular materials and the vacuoles originated from late endosome/lysosome as indicated by immunofluorescence studies. Instant calcium influx and calmodulin were required for the initiation of vacuole formation. The unique properties of these late endosome/lysosome-derived vacuoles were further discussed. In summary, cocaine elicited a new type of deregulated vacuole and the involvement of calcium/calmodulin in vacuolation could shed light on prevention or treatment of cocaine-induced cytotoxicity.
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Nantou, 545, Taiwan, ROC.
authors.forename: Chang-Tze R
authors.initials: CT
authors.lastname: Yu
authors.forename: Jih-Heng
authors.initials: JH
authors.lastname: Li
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Lih-Fang
authors.initials: LF
authors.lastname: Lin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002460:Cell Line; D003042:Cocaine / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D011992:Endosomes / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism* / Q000473:pathology
chemical_list: D002147:Calmodulin; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D002118:Calcium