Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular cAMP and calcium pathways in human adipocytes.
Biochemical and Biophysical Research Communications(2011)
摘要
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+)](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 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+)](i) and cAMP pathways and resultant downregulation of lipolysis key enzymes in adipocytes.
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关键词
CaSR,PVDF,GdCl3,BSA,PMSF,HEPES,PBS,Tris
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