title: BI-1 enhances Fas-induced cell death through a Na+/H+-associated mechanism.
abstract: The role of Bax inhibitor-1 (BI-1) in the protective mechanism against apoptotic stimuli has been studied; however, as little is known about its role in death receptor-mediated cell death, this study was designed to investigate the effect of BI-1 on Fas-induced cell death, and the underlying mechanisms. HT1080 adenocarcinoma cells were cultured in high concentration of glucose media and transfected with vector alone (Neo cells) or BI-1-vector (BI-1 cells), and treated with Fas. In cell viability, apoptosis, and caspase-3 analyses, the BI-1 cells showed enhanced sensitivity to Fas. Fas significantly decreased cytosolic pH in BI-1 cells, compared with Neo cells, and this decrease correlated with BI-1 oligomerization, mitochondrial Ca2+ accumulation, and significant inhibition of sodium-hydrogen exchanger (NHE) activity. Compared with Neo cells, a single treatment of BI-1 cells with the NHE inhibitor EIPA or siRNA against NHE significantly increased cell death, which suggests that the viability of BI-1 cells is affected by the maintenance of intracellular pH homeostasis through NHE.
authors: Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
authors: Geum-Hwa
authors: GH
authors: Lee
authors: Department of Dental Pharmacology, Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University, Iksan 570-749, Korea.
authors: Hyung-Ryong
authors: HR
authors: Kim
authors: Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
authors: Han-Jung
authors: HJ
authors: Chae
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; C491901:FAS protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D017923:Sodium-Hydrogen Exchangers; C484209:TMBIM6 protein, human; D019014:fas Receptor; D000584:Amiloride; D053148:Caspase 3; D002118:Calcium; C039614:ethylisopropylamiloride