Parathyroid hormone-related peptide is induced by stimulation of alpha 1A-adrenoceptors and improves resistance against apoptosis in coronary endothelial cells.
Parathyroid hormone-related peptide (PTHrP) is expressed throughout the vascular system, including coronary endothelial cells. The regulation of endothelial PTHrP expression and the role of PTHrP expression in endothelial cells is not clear. This study investigates the question of whether the stimulation of alpha-adrenergic or angiotensin II receptors increases endothelial expression of PTHrP and whether endogenously expressed PTHrP exerts intracrine effects in coronary endothelial cells. We found that the stimulation of alpha 1A-adrenoceptors, but not that of angiotensin II, increases cellular expression of PTHrP in growing, but not in growth-arrested, coronary endothelial cells. Angiotensin II increases the expression of PTHrP in smooth muscle cells but not in endothelial cells. PTHrP enters the nucleus of endothelial cells at the stadium of confluence, which suggests an intracrine effect of PTHrP. It was further investigated whether the down-regulation of endogenous PTHrP expression by transfection with antisense oligonucleotides alters cell proliferation or apoptosis resistance in growing or nongrowing endothelial cells. Down-regulation of PTHrP did not modify cell proliferation, but it increased the amount of UV-induced apoptosis. An increased expression of PTHrP in cells pretreated with an alpha-adrenoceptor agonist reduced the basal rate of apoptosis and improved resistance against UV-induced apoptosis. These results indicate a novel intracrine effect of PTHrP in coronary endothelial cells that improves cell survival. In endothelial cells, its expression is regulated by alpha-adrenoceptor stimulation in a cell-cycle-dependent and cell-type-specific manner.
Schorr
Katja
K
Physiologisches Institut, Justus-Liebig-Universität, Giessen, Germany.
Taimor
Gerhild
G
Degenhardt
Heike
H
Weber
Kerstin
K
Schlüter
Klaus-Dieter
KD
D000818:Animals; D017209:Apoptosis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D008297:Male; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism* / Q000502:physiology; D013347:Subcellular Fractions
D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine