Diflunisal inhibits prestin by chloride-dependent mechanism.
Diflunisal inhibits prestin by chloride-dependent mechanism.
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DOI：
10.1371/journal.pone.0183046
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Raphael RM
中科院分区：
文献类型：
--
作者：
Duret G;Pereira FA;Raphael RM
运动蛋白普雷斯廷是阴离子反向转运蛋白SLC 26家族的成员，并且对于耳蜗外毛细胞的电运动性和听力是必需的。唯一的直接抑制剂的电运动和相关的电荷转移是水杨酸，可能通过直接与阴离子结合位点上的普雷斯廷。在筛选其他普雷斯廷活性抑制剂时，我们探索了非甾体抗炎药二氟尼柳（diflunisal）的作用，二氟尼柳是水杨酸盐的衍生物。我们记录了普雷斯廷活性的全细胞膜片钳HEK细胞瞬时表达普雷斯廷和小鼠外毛细胞。我们监测了二氟尼柳对prestin依赖性非线性电容和电活动的影响。我们发现，二氟尼柳触发两个prestin相关的影响：氯离子独立增加的表面积和膜的比电容，和氯离子依赖性抑制的电荷转移和外毛细胞的电活动。我们的结论是，二氟尼柳影响细胞膜的组织和抑制prestin相关的电荷转移和电运动在生理氯化物浓度。考虑到二氟尼柳用于治疗神经退行性疾病的建议用途，对毛细胞功能的抑制作用值得注意。
The motor protein prestin is a member of the SLC26 family of anion antiporters and is essential to the electromotility of cochlear outer hair cells and for hearing. The only direct inhibitor of electromotility and the associated charge transfer is salicylate, possibly through direct interaction with an anion-binding site on prestin. In a screen to identify other inhibitors of prestin activity, we explored the effect of the non-steroid anti-inflammatory drug diflunisal, which is a derivative of salicylate. We recorded prestin activity by whole-cell patch clamping HEK cells transiently expressing prestin and mouse outer hair cells. We monitored the impact of diflunisal on the prestin-dependent non-linear capacitance and electromotility. We found that diflunisal triggers two prestin-associated effects: a chloride independent increase in the surface area and the specific capacitance of the membrane, and a chloride dependent inhibition of the charge transfer and the electromotility in outer hair cells. We conclude that diflunisal affects the cell membrane organization and inhibits prestin-associated charge transfer and electromotility at physiological chloride concentrations. The inhibitory effects on hair cell function are noteworthy given the proposed use of diflunisal to treat neurodegenerative diseases.
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影响因子：
120.7
作者：
Berk, John L.;Suhr, Ole B.;Obici, Laura;Sekijima, Yoshiki;Zeldenrust, Steven R.;Yamashita, Taro;Heneghan, Michael A.;Gorevic, Peter D.;Litchy, William J.;Wiesman, Janice F.;Nordh, Erik;Corato, Manuel;Lozza, Alessandro;Cortese, Andrea;Robinson-Papp, Jessica;Colton, Theodore;Rybin, Denis V.;Bisbee, Alice B.;Ando, Yukio;Ikeda, Shu-ichi;Seldin, David C.;Merlini, Giampaolo;Skinner, Martha;Kelly, Jeffery W.;Dyck, Peter J.
通讯作者：
Dyck, Peter J.
影响因子：
3.4
作者：
Fang, Jie;Iwasa, K. H.
通讯作者：
Iwasa, K. H.
影响因子：
5.5
作者：
Deák, L;Zheng, J;Dallos, P
通讯作者：
Dallos, P
影响因子：
7.3
作者：
Ertl, P;Rohde, B;Selzer, P
通讯作者：
Selzer, P
影响因子：
3.4
作者：
Lue, AJC;Zhao, HB;Brownell, WE
通讯作者：
Brownell, WE