Fas-induced apoptosis of glioma cells is associated with down-regulation of the hSCO1 protein, a subunit of complex IV.
ApoI/Fas belongs to the tumor necrosis factor receptor (TNFR) superfamily and mediates cell death in various cell types. Earlier studies from this laboratory have shown that Fas-mediated cell death of glioma cells occur, in part, through the production of reactive oxygen species (ROS). To further dissect the molecular mechanisms that are involved in Fas-induced cell death, we compared gene expression between Fas-treated and saline-treated human neuroglioma H4 cells by using the technique of mRNA differential display. This approach led to the identification of hSCO1, a component of the inner mitochondrial membrane, which is required for the correct assembly, and catalytic function of cytochrome-c oxidase, as a Fas down-regulated gene. The decrease in hSCO1 mRNA expression was time-dependent, becoming most prominent after 4 h of Fas-treatment. Morphological changes observed by confocal microscopy revealed that after 4 h of Fas-treatment, the cells undergo membrane blebbing and early formation of apoptotic bodies. These observations are discussed in terms of their support for an important role of mitochondrial events in Fas-induced apoptosis.
Jayanthi
S
S
Molecular Neuropsychiatry Section, NIDA-IRP, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Lewis
B D
BD
Cadet
J L
JL
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D015152:Blotting, Northern; D015536:Down-Regulation / Q000502:physiology; D003576:Electron Transport Complex IV / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000502:physiology; D018832:Molecular Chaperones; D009457:Neuroglia / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; C489345:SCO1 protein, human; D019014:fas Receptor; D003576:Electron Transport Complex IV