Characterization of cocaine-elicited cell vacuolation: the involvement of calcium/calmodulin in organelle deregulation.
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.
Yu
Chang-Tze R
CT
Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Nantou, 545, Taiwan, ROC.
Li
Jih-Heng
JH
Lee
Te-Chang
TC
Lin
Lih-Fang
LF
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
D002147:Calmodulin; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D002118:Calcium