Correlation of intracellular diadenosine triphosphate (Ap3A) with apoptosis in Fhit-positive HEK293 cells.
The pro-apoptotic Fhit tumor suppressor protein binds and hydrolyses diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) in vitro. We have measured the level of both these nucleotides in Fhit-positive HEK293 cells exposed to various apoptosis inducers. Cold shock, anti-Fas, cadmium ions and etoposide all increased the basal level of Ap4A of 0.500pmol/10(6)cells by about 50%. However, the corresponding increases in Ap3A from a basal 0.079pmol/10(6)cells correlated closely with the degree of apoptosis produced, up to a maximum of 0.510pmol/10(6)cells with etoposide. These results support the view that Ap3A is the in vivo Fhit ligand and that an inhibition of Fhit activity is a key element in Fhit-mediated apoptosis.
Fisher
David I
DI
Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK.
McLennan
Alexander G
AG
D000085:Acetates / Q000494:pharmacology; D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology; D002460:Cell Line; D003080:Cold Temperature; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009363:Neoplasm Proteins / Q000378:metabolism*; D009997:Osmotic Pressure; D015398:Signal Transduction / Q000187:drug effects; D013012:Sorbitol / Q000494:pharmacology; D015854:Up-Regulation; D019014:fas Receptor / Q000276:immunology; D000099170:Bis(5'-adenosyl)triphosphatase
D000085:Acetates; D017766:Acid Anhydride Hydrolases; D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic; D002104:Cadmium; D015226:Dinucleoside Phosphates; D005047:Etoposide; D008024:Ligands; D009363:Neoplasm Proteins; D013012:Sorbitol; D019014:fas Receptor; D000099170:Bis(5'-adenosyl)triphosphatase; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; C028031:cadmium acetate