Yonezawa Tomo, Kobayashi Yosuke, Obara Yoshiaki
Department of Animal Physiology, Graduate School of Agricultural Science, Tohoku University, Amamiyamachi, Sendai 981-8555, Japan.
Cell Signal. 2007 Jan;19(1):185-93. doi: 10.1016/j.cellsig.2006.06.004. Epub 2006 Aug 2.
The expression of GPR41 and 43, which have recently been identified as G-protein-coupled cell-surface receptors for short-chain fatty acids (SCFAs), was detected in a human breast cancer cell line (MCF-7) by RT-PCR. Acetate, propionate and butyrate induced an increase in intracellular Ca2+ in these cells that was not blocked by treatment with pertussis toxin (PTX). SCFAs significantly reduced forskolin-induced cAMP levels in these cells. The phosphorylation of mitogen-activated protein kinase (MAPK) p38 was selectively increased by SCFAs. The downstream substrate heat shock protein 27 (HSP27) was also phosphorylated by SCFAs at Ser-78 and-82, but not-15. Propionate induced elevations in intracellular Ca2+ and the phosphorylation of p38 were inhibited by the silencing of GPR43 using a specific siRNA. These results suggest that GPR41 and 43 mediate SCFA signaling in mammary epithelial cells and thereby play an important role in their stress management.
GPR41和43最近被确定为短链脂肪酸（SCFAs）的G蛋白偶联细胞表面受体，通过逆转录聚合酶链反应（RT-PCR）在人乳腺癌细胞系（MCF-7）中检测到它们的表达。乙酸盐、丙酸盐和丁酸盐可使这些细胞内的细胞内Ca2+增加，而百日咳毒素（PTX）处理并不能阻断这种增加。短链脂肪酸可显著降低这些细胞中福斯高林诱导的环磷酸腺苷（cAMP）水平。短链脂肪酸可选择性增加丝裂原活化蛋白激酶（MAPK）p38的磷酸化。下游底物热休克蛋白27（HSP27）在Ser-78和-82位点也被短链脂肪酸磷酸化，但在-15位点未被磷酸化。使用特异性小干扰RNA（siRNA）沉默GPR43可抑制丙酸盐诱导的细胞内Ca2+升高和p38的磷酸化。这些结果表明，GPR41和43介导乳腺上皮细胞中的短链脂肪酸信号传导，从而在其应激管理中发挥重要作用。
