Reduced Capacitative Calcium Entry Correlates with Vesicle Accumulation and Apoptosis

• Published in: The Journal of biological chemistry Vol. 274; no. 12; pp. 8261 - 8268
• Main Authors: Jayadev, S, Petranka, J G, Cheran, S K, Biermann, J A, Barrett, J C, Murphy, E
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 19-03-1999
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Apoptosis; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Cell Line; Cricetinae; Cytoplasm - metabolism; DNA Fragmentation; Hydrogen-Ion Concentration; Imidazoles - pharmacology; Macrolides; Mesocricetus; Organelles - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.12.8261

A preneoplastic variant of Syrian hamster embryo cells, sup(+), exhibits decreased endoplasmic reticulum calcium levels and
subsequently undergoes apoptosis in low serum conditions (Preston, G. A., Barrett, J. C., Biermann, J. A., and Murphy, E.
(1997) Cancer Res . 57, 537–542). This decrease in endoplasmic reticulum calcium appears to be due, at least in part, to reduced capacitative
calcium entry at the plasma membrane. Thus we investigated whether inhibition of capacitative calcium entry per se could reduce endoplasmic reticulum calcium and induce apoptosis of cells. We find that treatment with either SKF96365 (30–100
μ m ) or cell-impermeant 1,2-bis( o -amino-5-bromophenoxy)ethane- N,N,N′,N′ -tetraacetic acid (5–10 m m ) is able to induce apoptosis of cells in conditions where apoptosis does not normally occur. Because previous work has implicated
vesicular trafficking as a mechanism of regulating capacitative calcium entry, we investigated whether disruption of vesicular
trafficking could lead to decreased capacitative calcium entry and subsequent apoptosis of cells. Coincident with low serum-induced
apoptosis, we observed an accumulation of vesicles within the cell, suggesting deregulated vesicle trafficking. Treatment
of cells with bafilomycin (30–100 n m ), an inhibitor of the endosomal proton ATPase, produced an accumulation of vesicles, decreased capacitative entry, and induced
apoptosis. These data suggest that deregulation of vesicular transport results in reduced capacitative calcium entry which
in turn results in apoptosis.