Format

Send to

Choose Destination
See comment in PubMed Commons below
Int J Mol Med. 2009 Sep;24(3):373-80.

Activation of the receptor for parathyroid hormone and parathyroid hormone related protein induces apoptosis via the extrinsic and intrinsic signaling pathway.

Author information

1
Department of Internal Medicine IV, Hepatology and Gastroenterology, University Hospital, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.

Abstract

Parathyroid hormone (PTH) is the primary regulator of serum calcium homeostasis and bone metabolism. PTH acts primarily by binding to its receptor, PTH1R, in the bone and kidney. In addition to PTH, PTH1R also recognizes PTH-related peptide (PTHrP), a paracrine/autocrine factor originally described as the hormone responsible for hypercalcemia of malignancy. PTHrP is developmentally regulated and expressed, and it has been shown to play a physiological role in development, differentiation, cell proliferation and survival. We investigated the effects of PTH1R activation on the apoptosis signaling programs of human embryonic kidney (HEK) cells. Stimulation experiments of the CD95, TNF-R and TRAIL-R death receptor systems revealed that activation of PTH1R in HEK cells triggers signaling via each of these death receptors. Furthermore, our findings demonstrate a link between activation of PTH1R and the mitochondrial apoptosis pathway. PTHR1R overexpression led to an alteration of the mitochondrial membrane potential and activation of the intrinsic apoptosis signaling pathway. Our data indicate that activation of PTH1R engages major apoptosis signaling pathways by inducing signaling via death receptors and mitochondria in HEK cells. Thus, beyond its importance in development and differentiation, we describe an important role for the PTH/PTHrP receptor system in apoptosis of differentiating/embryonic cells.

PMID:
19639230
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Spandidos Publications
    Loading ...
    Support Center