Carboxy-terminal PTH fragments stimulate [3H]thymidine incorporation in vascular endothelial cells.
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.
Ding
Ke-Hong
KH
Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia, CB-2803, 1120, 15th Street, Augusta, GA 30912, USA.
Zhong
Qing
Q
Xie
Ding
D
Xu
Jianrui
J
Bollag
Roni J
RJ
Bollag
Wendy B
WB
Isales
Carlos M
CM
D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D010281:Parathyroid Hormone / Q000737:chemistry* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D000096926:Benzenesulfonamides
D001596:Benzylamines; D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D013936:Thymidine; C503960:parathyroid hormone (73-84); C072105:KN 93; D000096926:Benzenesulfonamides