| S-nitrosoglutathione reductase alleviates morphine analgesic tolerance by restricting PKCα S-nitrosation☆ |
| Su, LY; Jiao, LJ; Liu, QJ; Qiao, XH; Xie, T; Ma, ZY; Xu, M; Ye, MS; Yang, LX; Chen, C; Yao, YG
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| 2024
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| 发表期刊 | REDOX BIOLOGY
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| ISSN | 2213-2317
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| 卷号 | 75 |
| 摘要 | Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the downregulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuronspecific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKC alpha) at the Cys78 and Cys132 sites, leading to inhibition of PKC alpha kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKC alpha S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance. |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14500
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| 专题 | 科研部门_疾病机理遗传学和进化医学学科组（姚永刚）
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推荐引用方式
GB/T 7714 |
Su, LY,Jiao, LJ,Liu, QJ,et al. S-nitrosoglutathione reductase alleviates morphine analgesic tolerance by restricting PKCα S-nitrosation☆[J]. REDOX BIOLOGY,2024,75.
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| APA |
Su, LY.,Jiao, LJ.,Liu, QJ.,Qiao, XH.,Xie, T.,...&Yao, YG.(2024).S-nitrosoglutathione reductase alleviates morphine analgesic tolerance by restricting PKCα S-nitrosation☆.REDOX BIOLOGY,75.
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| MLA |
Su, LY,et al."S-nitrosoglutathione reductase alleviates morphine analgesic tolerance by restricting PKCα S-nitrosation☆".REDOX BIOLOGY 75(2024).
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