Individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity in dexamethasone-treated rat osteoblastic osteosarcoma cells, ROS 17/2.8.
The individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity were examined in dexamethasone-treated rat osteoblastic osteosarcoma cells ROS 17/2.8. Dexamethasone-induced alkaline phosphatase activity was inhibited not only by hPTH(1-84) and amino-terminal PTH fragment hPTH(1-34), but also by carboxyl-terminal PTH fragment hPTH(69-84) in a dose-related fashion. At 10(-7) mol/l, hPTH(1-84) completely abolished dexamethasone-induced alkaline phosphatase activity, while hPTH(1-34) and hPTH(69-84) reduced alkaline phosphatase activity to 0.16 +/- 0.02 and 0.80 +/- 0.03 fold, respectively, of the control value obtained in the absence of PTH peptides. The combination of hPTH(1-34) and hPTH(69-84) resulted in reduction of alkaline phosphatase activity to the level obtained by hPTH(1-84). The shorter carboxyl-terminal PTH fragment hPTH(71-84) did not affect alkaline phosphatase activity or modulate the action of hPTH(1-34). The longer carboxyl-terminal PTH fragment hPTH(53-84) stimulated alkaline phosphatase activity up to 1.23 +/- 0.03 fold and partially blunted the inhibitory effect of hPTH(1-34) on alkaline phosphatase activity. These findings suggest that carboxyl-terminal PTH fragments could exert diverse effects on the target cells, depending on the length of deletion of amino-terminal amino acids of PTH molecule, and interact with amino-terminal PTH fragment. The two amino-terminal amino acids of hPTH(69-84) and the 53-68 portion of hPTH(53-84) might be responsible for the respective inhibitory and stimulatory effects of the peptides on alkaline phosphatase activity.
Nakamoto
C
C
Department of Medicine, Kobe University School of Medicine, Japan.
Baba
H
H
Fukase
M
M
Nakajima
K
K
Kimura
T
T
Sakakibara
S
S
Fujita
T
T
Chihara
K
K
D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D002118:Calcium / Q000502:physiology; D003907:Dexamethasone; D004305:Dose-Response Relationship, Drug; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D019379:Teriparatide; D013997:Time Factors; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D002118:Calcium