Genistein Suppressing the ROS-Induced Hypersensitivity of Rat Vagal Lung C-Fiber Afferents through an ERα-Mediated Mechanism

Chou-Ming Yeh ； Yu-Jung Lin ； Tien-Huan Hsu ； Ting Ruan

《The Chinese Journal of Physiology》 61卷1期 (2018/02) Pp. 14-24

https://doi.org/10.4077/CJP.2018.BAG518

摘要

Reactive oxygen species (ROS) may induce hypersensitivity of vagal lung C-fibers (VLCFs) through the interaction of transient receptor potential ankyirn 1 (TRPA1) and P2X receptors. Genistein is a soy-derived isoflavone that exerts antioxidant effects by binding to estrogen receptors (ERs), ERα and ERβ. We investigated whether ER activation by genistein can suppress H_2O_2-mediated VLCF hypersensitivity and identified the types of ERs involved. Results revealed that subcutaneous injection of genistein or 4,4',4＂-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, a selective ERα agonist) can attenuate H_2O_2-induced VLCF hypersensitivity. The suppressive effects of genistein and PPT were inhibited by an additional treatment with ICI182780 (a nonselective ER antagonist) or 1,3-bis(4- hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP, a selective ERα antagonist). Treatment with a combination of PPT, HC030031 (a TRPA1 receptor antagonist), and iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS, a P2X receptor antagonist) did not further inhibit H_2O_2-induced VLCF hypersensitivity as compared with combined HC030031 and iso-PPADS treatment. In conclusion, ERα activation by genistein can suppress H_2O_2- induced VLCF hypersensitivity through its functional interaction with TRPA1 and P2X receptors.

關鍵字

airway hypersensitivity ； estrogen receptor ； genistein ； vagal lung C-fiber

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