Endothelin attenuates apoptosis in human smooth muscle cells.
An imbalance between proliferation and apoptosis is an important causal factor for disorders involving abnormal cell accumulation. Endothelin (ET)-1, a 21-amino-acid peptide with mitogenic and vasoconstricting activities, not only acts as a mitogen, but also attenuates paclitaxel-induced apoptosis in smooth muscle cells. In both human pericardial and prostatic smooth muscle cells, addition of ET-1 reduced paclitaxel-induced DNA fragmentation and phosphatidylserine on the cell surface, two characteristics of apoptosis. By comparison, angiotensin II, another vasoactive peptide, did not have a significant effect on apoptosis. The effect of ET-1 was dose-dependent with an EC50 of 1 nM. These results suggest that ET is a potential survival factor for smooth muscle cells, and that altered activity of the ET system in disease states has potential to contribute to aberrant cell growth.
Wu-Wong
J R
JR
Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA.
Chiou
W J
WJ
Dickinson
R
R
Opgenorth
T J
TJ
D000804:Angiotensin II / Q000494:pharmacology; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D000077868:Atrasentan; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D017239:Paclitaxel / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010496:Pericardium; D010718:Phosphatidylserines / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D011467:Prostate; D011759:Pyrrolidines / Q000494:pharmacology
D017304:Annexin A5; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010718:Phosphatidylserines; D011759:Pyrrolidines; D000804:Angiotensin II; D011419:Propidium; D017239:Paclitaxel; D000077868:Atrasentan