Rescue of trophoblast apoptosis by parathyroid hormone-related protein.

Abstract

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.