Rescue of trophoblast apoptosis by parathyroid hormone-related protein.
The effects of the 1-34 N-terminal parathyroid hormone-related protein fragment (0-10 microM) and the 67-86 parathyroid hormone-related protein fragment (0-10 microM) on trophoblast apoptosis, induced by TNFalpha and IFN-gamma or by the protein kinase inhibitor staurosporine, were investigated. TNFalpha/IFN-gamma and staurosporine significantly increased the rate of apoptosis by fivefold and by eightfold, respectively. Parathyroid hormone-related protein (1-34) evoked a dose-dependent rescue of both TNFalpha/IFNgamma-induced and staurosporine-induced apoptosis, whereas parathyroid hormone-related protein (67-86) had no significant effect on staurosporine-induced apoptosis, and only significantly diminished TNFalpha/IFNgamma-induced apoptosis at 10 microM. Parathyroid hormone-related protein was thus found to be a cytotrophoblast apoptosis survival factor.
Crocker
Ian
I
Department of Obstetrics and Gynaecology, School of Human Development, City Hospital, Nottingham, UK.
Kaur
Malveen
M
Hosking
David J
DJ
Baker
Philip N
PN
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D011247:Pregnancy / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004791:Enzyme Inhibitors; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019311:Staurosporine