Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, China.
Biochem Biophys Res Commun. 2011 Jan 7;404(1):393-9. doi: 10.1016/j.bbrc.2010.11.129. Epub 2010 Dec 3.
The calcium-sensing receptor (CaSR) was cloned initially from the bovine parathyroid and its primary physiological role is maintaining constant blood Ca(2+) 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 GdCl(3), a CaSR agonist. CaSR stimulation decreased both cyclic AMP (cAMP) level and cAMP-dependent protein kinase A (PKA) activity. GdCl(3) treatment led to an increase in intracellular calcium (Ca(2+)) 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 GdCl(3). 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 Ca(2+) and cAMP pathways and resultant downregulation of lipolysis key enzymes in adipocytes.
钙敏感受体（CaSR）最初从牛甲状旁腺中克隆，其主要生理作用是维持血液 Ca(2+)水平的恒定。随后，在人脂肪组织中发现 CaSR 的表达，但它的生理功能仍不清楚。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 被其激动剂 GdCl(3)激活后对脂肪分解有抑制作用。CaSR 刺激降低了环磷酸腺苷 (cAMP)水平和 cAMP 依赖性蛋白激酶 A (PKA)活性。GdCl(3)处理导致细胞内钙离子 (Ca(2+))增加和磷酸二酯酶 3B (PDE3B)mRNA 水平升高。此外，用 GdCl(3)处理可下调脂肪分解的下游关键酶 HSL 和 ATGL 的转录和翻译水平。与对照组相比，CaSR 拮抗剂 NPS2390 或 CaSR 小干扰 RNA (siRNA)基因沉默可预防上述作用。这些发现表明，CaSR 通过介导潜在的 Ca(2+)和 cAMP 途径以及脂肪细胞中脂肪分解关键酶的下调，发挥抗脂肪分解作用。
