کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8538742 | 1561119 | 2018 | 44 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of NLRX1-mediated autophagy accelerates the ototoxic potential of cisplatin in auditory cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member Ã1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus. We found that NLRX1 expression was increased concurrent with the increase of autophagy activation in HEI-OC1 cells under the cisplatin insult. NLRX1 overexpression led to the amount of accumulation of autophagsomes in HEI-OC1 cells in normal condition and a higher activation of autophagy concurrent with cell injury in HEI-OC1 cells treated with cisplatin, whereas, NLRX1 silencing decreased the activation level of autophagy concurrent with increased cell viability in HEI-OC1 cells treated with cisplatin. Mechanistic studies showed that NLRX1 potentiated mitochondrial-derived ROS generation in response to cisplatin exposure. Inhibition of ROS generation significantly prevented autophagy activation and apoptosis both in HEI-OC1cells and cochlear explants treated with cisplatin. The findings from this work reveal that NLRX1 sensitizes auditory cells in vitro to cisplatin-induced ototoxity via autophagic cell death pathway, providing another strategy against cisplatin-induced ototoxity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 343, 15 March 2018, Pages 16-28
Journal: Toxicology and Applied Pharmacology - Volume 343, 15 March 2018, Pages 16-28
نویسندگان
Haiyan Yin, Qianqian Yang, Zhixin Cao, Hongrui Li, Zhaoyan Yu, Guodong Zhang, Gaoying Sun, Rongjun Man, Haibo Wang, Jianfeng Li,