Short carboxyl terminal parathyroid hormone peptides modulate human parathyroid hormone signaling in mouse osteoblasts.
Short carboxyl terminal parathyroid hormone peptides modulate human parathyroid hormone signaling in mouse osteoblasts.
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DOI：
10.1016/j.bbrc.2021.07.085
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发表时间：
2021-10-01
影响因子：
3.1
通讯作者：
Kumar R
中科院分区：
文献类型：
--
作者：
Kritmetapak K;Singh RJ;Craig TA;Hines JM;Kumar R
通过液相色谱-高分辨率质谱分析，最近在肾功能正常、慢性肾衰竭和终末期肾病患者的血清中鉴定出了生物活性未知的新型人甲状旁腺激素（hPTH）肽。为了确定这些肽的生物活性，我们通过固相肽合成法合成了hPTH 28 -84、hPTH 38 -84和hPTH 45 -84肽，并通过评估3 ′，5 ′-环腺苷酸（cAMP）的积累和碱性磷酸酶活性的诱导，单独或与天然激素hPTH 1 -84一起在MC 3 T3-E1小鼠成骨细胞中测试了它们的生物活性。增加剂量的hPTH 1 -84（1-100 nM）增加了成骨细胞中cAMP和碱性磷酸酶活性的积累。浓度为1-100 nM的hPTH 28 -84、hPTH 38 -84和hPTH 45 -84是生物惰性的。令人惊讶的是，100 nM hPTH 38 -84和hPTH 45 -84增加了用增加量的hPTH 1 -84处理的成骨细胞中cAMP的积累。人PTH 28 -84单独或与hPTH 1 -84组合对cAMP活性没有影响。相反，100 nM hPTH 38 -84、hPTH 45 -84和hPTH 28 -84阻断了hPTH 1 -84对碱性磷酸酶活性的激活。数据显示，与单独的全长hPTH 1 -84相比，短羧基末端hPTH肽hPTH 38 -84和hPTH 45 -84增加了培养的成骨细胞中响应于用全长hPTH 1 - 84处理而产生的细胞cAMP的量。人PTH 28 -84单独或与hPTH 1 -84组合对cAMP活性没有影响。与单独的hPTH 1 -84相比，人PTH 28 -84、hPTH 38 -84和hPTH 45 -84降低了hPTH 1 - 84在成骨细胞中诱导碱性磷酸酶活性的作用。人PTH的短羧基肽是生物惰性的，但当与全长hPTH 1 -84一起施用时，调节hPTH 1 -84在成骨细胞中的生物活性。
Novel human parathyroid hormone (hPTH) peptides of unknown biological activity have recently been identified in the serum of subjects with normal renal function, chronic renal failure, and end-stage renal disease through the application of liquid chromatography-high resolution mass spectrometry. To determine the bioactivity of these peptides, we synthesized hPTH28–84, hPTH38–84, and hPTH45–84 peptides by solid phase peptide synthesis and tested their bioactivity in MC3T3-E1 mouse osteoblasts, either individually or together with the native hormone, hPTH1–84, by assessing the accumulation of 3´,5´-cyclic adenosine monophosphate (cAMP) and the induction of alkaline phosphatase activity. Increasing doses of hPTH1–84 (1–100 nM) increased the accumulation of cAMP and alkaline phosphatase activity in osteoblasts. hPTH28–84, hPTH38–84, and hPTH45–84 in concentrations of 1–100 nM were biologically inert. Surprisingly, 100 nM hPTH38–84 and hPTH45–84 increased the accumulation of cAMP in osteoblasts treated with increasing amounts of hPTH1–84. Human PTH28–84 had no effects on cAMP activity alone or in combination with hPTH1–84. Conversely, 100 nM hPTH38–84, hPTH45–84, and hPTH28–84 blocked the activation of alkaline phosphatase activity by hPTH1–84. The data show that the short carboxyl-terminal hPTH peptides, hPTH38–84 and hPTH45–84, increase the amount of cellular cAMP generated in cultured osteoblasts in response to treatment with full-length hPTH1–84 when compared to full-length hPTH1–84 alone. Human PTH28–84 had no effect on cAMP activity alone or in combination with hPTH1–84. Human PTH28–84, hPTH38–84 and hPTH45–84 reduced the effects of hPTH1–84 in osteoblasts with respect to the induction of alkaline phosphatase activity compared to hPTH1–84 alone. Short carboxyl peptides of human PTH are biologically inert but when administered together with full-length hPTH1–84 modulate the bioactivity of hPTH1–84 in osteoblasts.
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影响因子：
--
作者：
DAMOUR, P;HUET, PM;ROSENBLATT, M
通讯作者：
ROSENBLATT, M
影响因子：
2.3
作者：
Kritmetapak K;Losbanos L;Berent TE;Ashrafzadeh-Kian SL;Algeciras-Schimnich A;Hines JM;Singh RJ;Kumar R
通讯作者：
Kumar R
影响因子：
4
作者：
BRINGHURST, FR;STERN, AM;POTTS, JT
通讯作者：
POTTS, JT
影响因子：
5.8
作者：
D'Amour, P;Räkel, A;Cantor, T
通讯作者：
Cantor, T
DOI：
10.1083/jcb.80.3.715
发表时间：
1979-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Habener JF;Amherdt M;Ravazzola M;Orci L
通讯作者：
Orci L