Sulforaphane attenuates cisplatin-induced hearing loss by inhibiting histone deacetylase expression.
Sulforaphane attenuates cisplatin-induced hearing loss by inhibiting histone deacetylase expression.
复制标题
DOI：
10.1177/20587384211034086
复制
发表时间：
2021-01
影响因子：
3.5
通讯作者：
Chen FQ
中科院分区：
文献类型：
--
作者：
Wang J;Tian KY;Fang Y;Chang HM;Han YN;Chen FQ
十字花科蔬菜富含萝卜硫素(SFN)，它是一种天然的HDAC抑制剂(HDACi)。我们先前的研究发现，HDACi可以恢复组蛋白乙酰转移酶/组蛋白脱乙酰基酶(HAT/HDAC)的平衡，减轻庆大霉素所致的豚鼠听力损失。在此，我们研究了三七总皂苷对顺铂所致听力损失(CIHL)的保护作用。将30只大鼠随机分为3组：对照组、顺铂组、三七总皂甙+顺铂组。给大鼠注射三七总皂苷(30 mg/kg，1次/d)和顺铂(7 mg/kg，2次/d)，连续7天，观察三七总皂苷对脑损伤的保护作用。观察大鼠听性脑干反应(ABR)阈值漂移和免疫组织化学染色的耳蜗基底膜。在体外实验中，我们用SFN(5，10和15μM)和顺铂(10μM)处理HEI-OC1细胞和大鼠耳蜗器型培养物。免疫荧光、细胞活力和蛋白质分析进一步分析SFN对CIHL的保护作用机制。SFN(30 mg/kg，每天1次)可减少顺铂(7 mg/kg，每天2次)引起的ABR阈值漂移和外毛细胞丢失。CCK-8实验显示，顺铂(10μM)可使HeI-Oc1细胞存活率降低42%，且三七总碱具有剂量依赖性保护作用。在耳蜗器型培养中，我们发现SFN(10和15μM)增加了顺铂(10μM)诱导的肌球蛋白7a+细胞计数，并恢复了纤毛的形态。SFN(5，10和15μM)逆转顺铂(10μM)诱导的HDAC2，-4和-5的增加，SFN(15μM)逆转顺铂(10μM)诱导的H3-Ack9[乙酰组蛋白H3(Lys9)]蛋白表达的下降。顺铂或顺铂联合SFN均不影响HDAC7或HDAC9的表达。三七总皂苷可阻止HAT/HDAC平衡的破坏，从而保护大鼠免受CIHL的影响。
Cruciferous vegetables are a rich source of sulforaphane (SFN), which acts as a natural HDAC inhibitor (HDACi). Our previous study found that HDACi could restore histone acetyltransferase/histone deacetylase (HAT/HDAC) balance in the cochlea and attenuate gentamicin-induced hearing loss in guinea pigs. Here, we investigated the protective effect of SFN on cisplatin-induced hearing loss (CIHL). Thirty rats were randomly divided into 3 equal groups: the control group, cisplatin group, and SFN+cisplatin group. Rats were injected with SFN (30 mg/kg once a day) and cisplatin (7 mg/kg twice a day) for 7 days to investigate the protective role of SFN on CIHL. We observed auditory brainstem response (ABR) threshold shifts and immunostained cochlear basilar membranes of rats. For in vitro experiments, we treated HEI-OC1 cells and rat cochlear organotypic cultures with SFN (5, 10, and 15 μM) and cisplatin (10 μM). Immunofluorescence, cell viability, and protein analysis were performed to further analyze the protective mechanism of SFN on CIHL. SFN (30 mg/kg once a day) decreased cisplatin (7 mg/kg twice a day)-induced ABR threshold shifts and outer hair cell loss. CCK-8 assay showed that cisplatin (10 μM) reduced the viability of HEI-OC1 cells to 42%, and SFN had a dose-dependent protective effect. In cochlear organotypic cultures, we found that SFN (10 and 15 μM) increased cisplatin (10 μM)-induced myosin 7a+ cell count and restored ciliary morphology. SFN (5, 10, and 15 μM) reversed the cisplatin (10 μM)-induced increase in HDAC2, -4, and -5 and SFN (15 μM) reversed the cisplatin (10 μM)-induced decrease in H3-Ack9 [acetyl-histone H3 (Lys9)] protein expression in HEI-OC1 cells. Neither cisplatin nor cisplatin combined with SFN affected the expression of HDAC7, or HDAC9. SFN prevented disruption of the HAT/HDAC balance, protecting against CIHL in rats.
登录
查看更多内容
影响因子：
2.9
作者：
Kim YY;Nam H;Jung H;Kim B;Suh JG
通讯作者：
Suh JG
影响因子：
3.7
作者：
Royston KJ;Paul B;Nozell S;Rajbhandari R;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
25
作者：
Kros, CJ;Marcotti, W;Steel, KP
通讯作者：
Steel, KP
组蛋白脱乙酰酶抑制剂丁酸钠可减轻庆大霉素引起的体内听力损失
影响因子：
2.5
作者：
Wang, Jie;Wang, Ye;Chen, Fu-quan
通讯作者：
Chen, Fu-quan
HDAC 抑制剂丁酸钠可预防过敏性鼻炎并改变小鼠鼻粘膜中的 lncRNA 和 mRNA 表达谱
影响因子：
5.4
作者：
Wang, Jie;Cui, Mu;Chen, Fu-Quan
通讯作者：
Chen, Fu-Quan