Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line.
Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line.
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DOI：
10.1016/j.cellsig.2006.06.004
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发表时间：
2007
影响因子：
4.8
通讯作者：
T. Yonezawa;Yosuke Kobayashi;Y. Obara
中科院分区：
文献类型：
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作者：
T. Yonezawa;Yosuke Kobayashi;Y. Obara
利用RT-PCR技术，在人乳腺癌细胞系（MCF-7）中检测到GPR41和gpr43的表达，这两种蛋白最近被鉴定为短链脂肪酸（SCFAs）的g蛋白偶联细胞表面受体。醋酸盐、丙酸盐和丁酸盐诱导这些细胞中细胞内Ca2+的增加，这种增加不被百日咳毒素（PTX）治疗所阻断。SCFAs显著降低了这些细胞中福斯克林诱导的cAMP水平。scfa选择性地增加了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SCFAs磷酸化，但不被15位点磷酸化。丙酸诱导的细胞内Ca2+的升高和p38的磷酸化可以通过使用特定的siRNA沉默GPR43来抑制。这些结果表明，GPR41和43介导乳腺上皮细胞的SCFA信号传导，从而在其应激管理中发挥重要作用。
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.