Anion-exchange blocker enhances cytoplasmic vacuole formation and cell death in serum-deprived mouse kidney epithelial cells in mice.
An anion exchange blocker, DIDS, exhibits anti-apoptotic activity in response to several apoptotic stimuli, but has an opposite effect when apoptosis is induced by serum deprivation. After adding DIDS, serum-deprived MCT cells exhibited vacuole formation in their cytoplasm and underwent cell death. Caspase activity increased with the addition of DIDS to serum-deprived MCT cells, but Z-Asp-CH2-DCB, a caspase inhibitor, did not inhibit cell death in DIDS-treated, serum-deprived MCT cells. Cathepsin is considered to be important for vacuole formation and cell lysis, and pepstatin A, a cathepsin D inhibitor, partially inhibited vacuole formation in DIDS-treated, serum-deprived MCT cells, although caspase activation was not inhibited. 3-Methyladenin inhibited vacuole formation and cell death in DIDS-treated, serum-deprived MCT cells. These results suggest that DIDS-treated serum-deprived MCT cells undergo autophagy, not apoptosis.
Araki
Takashi
T
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. araki@minamitama.jp
Hayashi
Matsuhiko
M
Saruta
Takao
T
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000037:antagonists & inhibitors; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D004357:Drug Synergism; D004847:Epithelial Cells / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D044967:Serum / Q000378:metabolism*; D014617:Vacuoles / Q000502:physiology* / Q000648:ultrastructure
D000838:Anions; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid