The [53–63] amino acid portion of the parathyroid hormone molecule is essential for the stimulatory effect of carboxyl-terminal PTH fragments on alkaline phosphatase activity in dexamethasone-treated rat osteoblastic osteosarcoma cells, ROS 17/2.8

Abstract

Abstract:The effect of a series of truncated carboxyl-terminal parathyroid hormone (PTH) fragments on alkaline phosphatase (ALP) activity was further examined in dexamethasonetreated rat osteoblastic osteosarcoma cells, ROS 17/2.8. As we previously reported, dexamethasone-induced ALP activity was inhibited not only by hPTH (1-84) and aminoterminal PTH fragment hPTH (1-34), but also by carboxyl-terminal PTH fragment hPTH(69-84). The longer carboxyl-terminal PTH fragment hPTH (53-84) stimulated ALP activity, and the shorter carboxyl-terminal PTH fragment hPTH (71-84) did not affect ALP activity. The longest newly synthesized carboxyl-terminal PTH fragment hPTH (35-84), which is complementary to amino-terminal PTH fragment hPTH (1-34), stimulated ALP activity as potently as hPTH (53-84), but not more potently than hPTH (53-84). Another newly synthesized carboxyl-terminal PTH fragment hPTH (64-84), which has an intermediate peptide length between hFTH (53-84) and hPTH (69-84), inhibited ALP activity as potently as hPTH (69-84). These results suggest that the 35-52 amino acid portion of the PTH molecule might not be crucial for the stimulatory effect of carboxyl-terminal PTH fragments on ALP activity, and that the 53-63 portion, but not the 64-68 portion, of the PTH molecule might be essential for the stimulatory effect of carboxyl-terminal PTH fragments on ALP activity. Furthermore, the importance of the 69th and 70th amino acid of the PTH molecule for the inhibitory effect of carboxyl-terminal PTH fragments on ALP activity was confirmed.