Nakamoto C, Baba H, Fukase M, Nakajima K, Kimura T, Sakakibara S, Fujita T, Chihara K
Department of Medicine, Kobe University School of Medicine, Japan.
Acta Endocrinol (Copenh). 1993 Apr;128(4):367-72. doi: 10.1530/acta.0.1280367.
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.
在经地塞米松处理的大鼠成骨细胞骨肉瘤细胞ROS 17/2.8中，检测了完整甲状旁腺激素（PTH）、氨基端以及一系列截短的羧基端PTH片段对碱性磷酸酶活性的单独及联合作用。地塞米松诱导的碱性磷酸酶活性不仅受到人甲状旁腺激素（1-84）[hPTH(1-84)]和氨基端PTH片段hPTH(1-34)的抑制，还受到羧基端PTH片段hPTH(69-84)的剂量相关抑制。在10⁻⁷mol/L时，hPTH(1-84)完全消除了地塞米松诱导的碱性磷酸酶活性，而hPTH(1-34)和hPTH(69-84)分别将碱性磷酸酶活性降低至无PTH肽时对照值的0.16±0.02倍和0.80±0.03倍。hPTH(1-34)和hPTH(69-84)联合使用导致碱性磷酸酶活性降低至hPTH(1-84)所达到的水平。较短的羧基端PTH片段hPTH(71-84)不影响碱性磷酸酶活性，也不调节hPTH(1-34)的作用。较长的羧基端PTH片段hPTH(53-84)将碱性磷酸酶活性刺激至1.23±0.03倍，并部分减弱了hPTH(1-34)对碱性磷酸酶活性的抑制作用。这些发现表明，羧基端PTH片段可根据PTH分子氨基端氨基酸缺失的长度对靶细胞产生不同影响，并与氨基端PTH片段相互作用。hPTH(69-84)的两个氨基端氨基酸和hPTH(53-84)的53-68部分可能分别是这些肽对碱性磷酸酶活性产生抑制和刺激作用的原因。
