Opioids transiently prevent activation of apoptotic mechanisms following short periods of serum withdrawal.
Opioids exert a proapoptotic effect on several normal and tumoral cells. The aim of the present article was to examine the effect of opioids on the PC12 rat pheochromocytoma cell line, a model for the study of chromaffin cell apoptosis. These cells produce delta- and kappa-opioid agonists and their receptors. Our results were as follows: The kappa- and delta2-opioid receptor agonists had a rapid but transient effect on apoptosis at 3 h, whereas mu opioids did not. The effect of opioids was reversible by the opioid antagonists naloxone and nor-binaltorphimine. The effect of opioids was protective, suppressing serum deprivation-induced apoptosis to approximately 50% of controls. The protective effect of opioids on PC12 apoptosis was measurable only under serum deprivation. The effect of opioids was remarkably reproducible and highly constant in timing, which did not appear to depend on the duration of the preceding serum deprivation. Finally, opioids prevented the elevation of the Bcl-2 and Bak proteins following serum deprivation to the levels attained by serum supplementation. Our combined data suggest that opioids protect PC12 cells from entering a state of induced apoptosis following serum deprivation.
Dermitzaki
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Department of Clinical Chemistry, School of Medicine, University of Crete, Greece.
Chatzaki
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E
Gravanis
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Margioris
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AN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044482:Benzeneacetamides; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D016895:Culture Media, Serum-Free; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D008565:Membrane Proteins / Q000378:metabolism; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494774:Bak1 protein, rat; D044482:Benzeneacetamides; D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D009292:Narcotic Antagonists; D009294:Narcotics; D019253:Proto-Oncogene Proteins c-bcl-2; D011759:Pyrrolidines; D050998:bcl-2 Homologous Antagonist-Killer Protein; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; C045444:U 69593