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钙蛋白酶抑制剂N-乙酰亮氨酰-亮氨酰-正亮氨酸可减弱甲状旁腺激素诱导的MC3T3-E1成骨细胞收缩。

Parathyroid hormone-induced retraction of MC3T3-E1 osteoblastic cells is attenuated by the calpain inhibitor N-Ac-Leu-Leu-norleucinal.

作者信息

Murray E J, Tram K K, Murray S S, Lee D B

机构信息

Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Sepulveda, CA 91343.

出版信息

Metabolism. 1995 Feb;44(2):141-4. doi: 10.1016/0026-0495(95)90254-6.

DOI:10.1016/0026-0495(95)90254-6
PMID:7869906
Abstract

Parathyroid hormone (PTH) binding to its osteoblastic receptors stimulates cytoplasmic retraction within minutes. We hypothesized that the calpains (calcium-activated papain-like enzymes) contribute to PTH-induced osteoblastic retraction by catalyzing regulatory hydrolysis of cytoskeletal structural proteins or enzymes important in cytokinesis. N-Ac-Leu-Leu-norleucinal (ALLN), a reversible calpain inhibitor, was tested for its ability to inhibit PTH-induced retraction in murine MC3T3-E1 osteoblastic cells. ALLN inhibited PTH-induced retraction for 30 minutes in cells cultured on polystyrene cultureware or gelatin-coated glass cover slips, supporting the hypothesis that PTH-induced activation of the calpains contributes to short-term changes in MC3T3-E1 cell shape. Inhibition of PTH-induced retraction occurred on two substrata, suggesting that interactions between the extracellular matrix and cell surface proteins are not the sole determinants of morphology. Intracellular events, such as hydrolysis of focal adherens junction proteins on the cytoplasmic face of the plasma membrane, may contribute to PTH-induced retraction.

摘要

甲状旁腺激素(PTH)与其成骨细胞受体结合,在数分钟内即可刺激细胞质收缩。我们推测,钙蛋白酶(钙激活的木瓜蛋白酶样酶)通过催化细胞骨架结构蛋白或胞质分裂中重要酶的调节性水解,从而促进PTH诱导的成骨细胞收缩。N-乙酰亮氨酰-亮氨酰-正亮氨酸(ALLN)是一种可逆性钙蛋白酶抑制剂,我们测试了其抑制PTH诱导的小鼠MC3T3-E1成骨细胞收缩的能力。在聚苯乙烯培养器皿或明胶包被的玻璃盖玻片上培养的细胞中,ALLN可在30分钟内抑制PTH诱导的收缩,这支持了以下假说:PTH诱导的钙蛋白酶激活促成了MC3T3-E1细胞形状的短期变化。在两种基质上均发生了对PTH诱导收缩的抑制,这表明细胞外基质与细胞表面蛋白之间的相互作用并非形态的唯一决定因素。细胞内事件,例如质膜细胞质面粘着斑连接蛋白的水解,可能促成了PTH诱导的收缩。

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Parathyroid hormone-induced retraction of MC3T3-E1 osteoblastic cells is attenuated by the calpain inhibitor N-Ac-Leu-Leu-norleucinal.钙蛋白酶抑制剂N-乙酰亮氨酰-亮氨酰-正亮氨酸可减弱甲状旁腺激素诱导的MC3T3-E1成骨细胞收缩。
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Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3', 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cells.甲状旁腺激素通过增加成骨细胞MC3T3-E1细胞内3',5'-环磷酸腺苷的积累来增强骨形态发生蛋白活性。
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Distinct effects of calcium- and cyclic AMP-enhancing factors on cytoskeletal synthesis and assembly in mouse osteoblastic cells.钙和环磷酸腺苷增强因子对小鼠成骨细胞细胞骨架合成与组装的不同影响。
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Regulation of matrix Gla protein by parathyroid hormone in MC3T3-E1 osteoblast-like cells involves protein kinase A and extracellular signal-regulated kinase pathways.甲状旁腺激素对MC3T3-E1成骨样细胞中基质Gla蛋白的调节涉及蛋白激酶A和细胞外信号调节激酶途径。
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