Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.
Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.
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DOI：
10.1038/emm.2014.112
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发表时间：
2015-02-20
影响因子：
12.8
通讯作者：
Park, Raekil
中科院分区：
文献类型：
--
作者：
Kim, Se-Jin;Hur, Joon Ho;Park, Channy;Kim, Hyung-Jin;Oh, Gi-Su;Lee, Joon No;Yoo, Su-Jin;Choe, Seong-Kyu;So, Hong-Seob;Lim, David J.;Moon, Sung K.;Park, Raekil
风湿性关节炎的治疗方法有哪些？本研究探讨了布西拉明对顺铂诱导的大鼠（P2）和成年Balb/C小鼠听细胞、Corti器损伤的保护作用。顺铂增加了caspase-3和caspase-8蛋白酶的催化活性和自由基的产生，而这些活性和自由基的产生被布西拉明预处理显著抑制。布西拉明诱导Nrf 2的核内易位，从而增加γ-谷氨酰半胱氨酸合成酶（γ-GCS）和谷胱甘肽合成酶（GSS）的表达，进而诱导细胞内抗氧化剂谷胱甘肽（GSH）、血红素加氧酶1（HO-1）和超氧化物歧化酶2（SOD 2）。然而，HO-1和SOD 2的敲低研究表明，布西拉明对顺铂的保护作用是独立的HO-1和SOD的酶活性。此外，用布西拉明预处理保护Corti器官外植体上的感觉毛细胞免受顺铂诱导的细胞毒性，同时抑制半胱天冬酶-3活化。顺铂注射小鼠的脑干诱发反应显示出明显的听阈偏移增加，而在体内用布西拉明预处理可明显抑制听阈偏移。总之，布西拉明通过对自身的清除作用以及细胞内GSH的诱导来保护感觉毛细胞免受顺铂的影响。
Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.
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影响因子：
2.4
作者：
Choi, Byung-Min;Lim, Dai-Won;Kim, Bok-Ryang
通讯作者：
Kim, Bok-Ryang
影响因子：
2.8
作者：
Dickey, DT;Muldoon, LL;Neuwelt, EA
通讯作者：
Neuwelt, EA
影响因子：
2.8
作者：
Kamimura, T;Whitworth, CA;Rybak, LP
通讯作者：
Rybak, LP
影响因子：
64.5
作者：
HSU, HL;XIONG, J;GOEDDEL, DV
通讯作者：
GOEDDEL, DV
影响因子：
2.8
作者：
Kim, Se-Jin;Park, Channy;Park, Raekil
通讯作者：
Park, Raekil