Effect of transforming growth factor-beta on calcium homeostasis in prostate carcinoma cells.
Ca(2+) plays a fundamental role in the control of a variety of cellular functions, in particular, in energy metabolism and apoptosis. In this study, we show that TGF-beta at concentrations of 0.1-1.0 ng/ml transiently increases the level of intracellular Ca(2+) ([Ca(2+)](in)) in human prostate carcinoma, PC-3U, cells. Experiments with mitochondrial inhibitors (oligomycin and antimycin A) and an inhibitor of endoplasmic reticulum Ca(2+) uptake (BHQ) implied that the effect of TGF-beta1 was due to an effect on the mitochondria. TGF-beta1 treatment resulted in a decrease in ATP synthesis and to a depolarisation, leading to a release of Ca(2+) from mitochondria and decreased activity of the Ca(2+) pumps. Analysis of the mitochondria within the PC-3U cells by polarography and membrane potential-sensitive dye (Rhodamine 123) confirmed that under these experimental conditions, TGF-beta1 inhibited ATP synthesis and depolarised the mitochondria. The results implicate that TGF-beta1 affects the function of the mitochondria and may be of significance for the understanding of the proapoptotic effect of TGF-beta1 in these cells.
Biomedical Center, The Ludwig Institute for Cancer Research, Box 595, SE-751 24 Uppsala, Sweden.
Zemfira Z
ZZ
Gizatullina
Eva
E
Grapengiesser
Irina G
IG
Shabalina
Jan
J
Nedergaard
Carl-Henrik
CH
Heldin
Pontus
P
Aspenström
D000968:Antimycin A / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009840:Oligomycins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014475:Uncoupling Agents / Q000378:metabolism
D004791:Enzyme Inhibitors; D009840:Oligomycins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000968:Antimycin A; D000252:Calcium-Transporting ATPases; D010100:Oxygen; D002118:Calcium