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Nat Commun:GSTA4在能够减少铂耳毒性

2019-09-25 AlexYang MedSci原创

铂是最常用于癌症治疗的化疗药物之一。不幸的是,铂化疗的其中最主要的副作用是永久性的听力损失。最近,有研究人员表明了谷胱甘肽转移酶α4(GSTA4),Ⅱ期解毒酶超家族成员,能够通过益处雌性小鼠内耳的羟基壬烯醛(4-HNE)来减少铂产生的耳蜗毒性。在顺铂处理下,Gsta4功能的丧失能够导致雌性小鼠比雄性小鼠更加严重的听力损失。顺铂在雌性小鼠的内耳中能够刺激GSTA4的活性,而非雄性小鼠。在雌性Gsta

铂是最常用于癌症治疗的化疗药物之一。不幸的是,铂化疗的其中最主要的副作用是永久性的听力损失。

最近,有研究人员表明了谷胱甘肽转移酶α4(GSTA4),Ⅱ期解毒酶超家族成员,能够通过益处雌性小鼠内耳的羟基壬烯醛(4-HNE)来减少铂产生的耳蜗毒性。在顺铂处理下,Gsta4功能的丧失能够导致雌性小鼠比雄性小鼠更加严重的听力损失。顺铂在雌性小鼠的内耳中能够刺激GSTA4的活性,而非雄性小鼠。在雌性Gsta4-/-小鼠中,顺铂治疗能够导致耳蜗神经元中4-HNE水平的增加,而在雄性小鼠中不然。在CBA/CaJ小鼠中,卵巢切除术能够减少Gsta4的mRNA表达水平以及内耳中GSTA4的蛋白水平。

最后,研究人员指出,他们的发现表明了GSTA4依赖的去毒性在雌激素介导的神经保护中可能具有重要的作用。

原始出处:

Park HJ, Kim MJ, Rothenberger C et al. GSTA4 mediates reduction of cisplatin ototoxicity in female mice. Nat Commun. 12 Sep 2019

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    2019-10-22 liye789132251
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    2019-10-02 liuli5079
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