Carboxy-terminal PTH fragments stimulate [ 3H]thymidine incorporation in vascular endothelial cells

• Published in: Peptides (New York, N.Y. : 1980) Vol. 26; no. 5; pp. 853 - 862
• Main Authors: Ding, Ke-Hong, Zhong, Qing, Xie, Ding, Xu, Jianrui, Bollag, Roni J., Bollag, Wendy B., Isales, Carlos M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2005; Elsevier Science
• Subjects: Benzylamines - pharmacology; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Cell Proliferation - drug effects; Endothelial cells; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Humans; Parathyroid Hormone - chemistry; Parathyroid Hormone - pharmacology; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Proliferation; Protein Kinase Inhibitors - pharmacology; PTH; Receptors; Signaling; Sulfonamides - pharmacology; Thymidine - metabolism; Vertebrates: endocrinology; Signaling; Receptors; Proliferation; Calcium; PTH; Endothelial cells; Cell proliferation; Endothelial cell; Thymidine; Parathormone; Signal transduction; Parathyroid hormone; Biological receptor
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2005.01.002

We have previously reported that the intact PTH molecule (1–84) stimulates proliferation of human umbilical vein endothelial cells (HUVECs). To define the bioactive portion of the PTH molecule we utilized amino, mid and carboxy-terminal PTH fragments. Carboxy- but not amino-terminal fragments were equivalent to the intact PTH molecule in stimulating [ 3H]thymidine incorporation in HUVEC. Carboxy- but not amino-terminal PTH fragments increased intracellular calcium. Blocking the rise in intracellular calcium with calcium chelators abolished PTHs proliferative effect on HUVEC. In contrast to PTH 1–84, the carboxy-terminal fragment effect on [ 3H]thymidine incorporation was blocked by KN-93 an inhibitor of CaM kinase II. Taken together, these data suggest that the carboxy-terminal PTH is (or contains) the bioactive fragment responsible for the changes in intracellular calcium and thymidine incorporation in HUVEC stimulated with the intact PTH molecule.