Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular cAMP and calcium pathways in human adipocytes
Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular cAMP and calcium pathways in human adipocytes
复制标题
钙敏感受体通过细胞内 cAMP 和钙途径参与抑制人脂肪细胞的脂肪分解
DOI：
10.1016/j.bbrc.2010.11.129
复制
发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Sun, Changhao
中科院分区：
文献类型：
--
作者：
He, Yonghan;Zhang, Huaqi;Sun, Changhao
钙感应受体（CaSR）最初是从牛甲状旁腺中克隆出来的，其主要生理作用是维持恒定的血液Ca2+水平。随后。CaSR在人脂肪组织中表达，但其生理功能尚不清楚。本研究在SW872细胞中探讨了CaSR对脂肪分解的影响及其作用机制。结果表明，CaSR被CaSR激动剂GdCl3激活后，具有抑制脂肪分解的作用。CaSR刺激降低环AMP （cAMP）水平和cAMP依赖性蛋白激酶A （PKA）活性。GdCl3处理导致细胞内钙（[Ca2+](i)）和磷酸二酯酶3b (PDE3B) mRNA水平升高。此外，脂肪分解下游关键酶HSL和ATGL在转录和翻译水平上均被GdCl3下调。与对照组相比，上述效应可通过CaSR拮抗剂NPS2390或小干扰RNA （siRNA）沉默CaSR基因来阻止。这些发现表明，CaSR通过介导潜在的[Ca2+](i)和cAMP途径，以及由此导致的脂肪细胞中脂解关键酶的下调，发挥抗脂解作用。(C) 2011出版的爱思唯尔公司。
The calcium-sensing receptor (CaSR) was cloned initially from the bovine parathyroid and its primary physiological role is maintaining constant blood Ca2+ levels. Subsequently. CaSR was found to be expressed in human adipose tissue, however, its physiological functions remain unclear. In this study, the effect of CaSR on lipolysis and the mechanisms by which it functions were explored in SW872 cells. The results showed an inhibitory effect of CaSR on lipolysis after its being activated by GdCl3, a CaSR agonist. CaSR stimulation decreased both cyclic AMP (cAMP) level and cAMP-dependent protein kinase A (PKA) activity. GdCl3 treatment led to an increase in intracellular calcium ([Ca2+](i)) and mRNA level of phosphodiesterase3B (PDE3B). Furthermore, the downstream key enzymes of lipolysis, HSL and ATGL, were downregulated at both the transcription and translation levels by treatment with GdCl3. Compared to the control group, the above effects were prevented by either NPS2390, a CaSR antagonist, or CaSR gene silencing by small interfering RNA (siRNA). These findings suggest that CaSR plays an antilipolytic role by mediating potential [Ca2+](i) and cAMP pathways and resultant downregulation of lipolysis key enzymes in adipocytes. (C) 2011 Published by Elsevier Inc.