HIF-1α Ameliorates Diabetic Neuropathic Pain via Parkin-Mediated Mitophagy in a Mouse Model.
HIF-1α Ameliorates Diabetic Neuropathic Pain via Parkin-Mediated Mitophagy in a Mouse Model.
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在小鼠模型中，缺氧诱导因子-1α（HIF-1α）通过帕金（Parkin）介导的线粒体自噬改善糖尿病神经病理性疼痛。
DOI：
10.1155/2022/5274375
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发表时间：
2022
影响因子：
--
通讯作者：
Wang, Hanbing
中科院分区：
文献类型：
--
作者：
He, Jian;Qin, Zaisheng;Chen, Xin;He, Wanyou;Li, Donglin;Zhang, Lei;Le, Yue;Xiong, Qingming;Zhang, Bin;Wang, Hanbing
线粒体功能障碍在糖尿病神经病理性疼痛（DNP）中起着重要作用。线粒体自噬参与神经损伤引起的神经病理性疼痛已有报道。高血压和细胞缺氧是糖尿病的两个主要特征。缺氧诱导因子1α亚基（HIF-1α）在缺氧条件下线粒体稳态中发挥着至关重要的作用。然而，目前尚不清楚DNP中的线粒体自噬是否被改变以及是否受HIF-1α的调节。本研究结果显示，糖尿病小鼠脊髓线粒体自噬被激活，HIF-1α表达上调。HIF-1α激动剂二甲基草酰甘氨酸（DMOG）可进一步升高HIF-1α和Parkin蛋白，增强线粒体自噬，减轻线粒体功能障碍和痛觉过敏。此外，Park 2（编码Parkin）敲除加重糖尿病小鼠的痛觉过敏和线粒体功能障碍。此外，在Park 2 −/−糖尿病小鼠中，HIF-1α激动剂DMOG不能激活和诱导线粒体自噬。本研究首次证实HIF-1α可通过调节Parkin信号通路上调DNP小鼠脊髓线粒体自噬，为DNP的发病机制和治疗策略的研究提供新的思路。
Mitochondrial dysfunction, which can be regulated by mitophagy, plays a central role in diabetic neuropathic pain (DNP). Mitophagy that was involved in nerve damage-induced neuropathic pain has been reported. Hyperglycemia and cellular hypoxic were the two main characters of diabetes. Hypoxia-inducible factor 1α subunit (HIF-1α) plays a vital role in mitochondrial homeostasis under hypoxia. However, it remains unclear whether mitophagy was changed and could be regulated by HIF-1α in DNP. In this study, the results showed that mitophagy was activated and HIF-1α was upregulated in the spinal cord of diabetic mice. HIF-1α agonist dimethyloxalylglycine (DMOG) could further elevate HIF-1α and Parkin protein, enhance mitophagy, decrease mitochondrial dysfunction, and hyperalgesia. Furthermore, Park2 (encoding Parkin) knockout aggravated hyperalgesia and mitochondrial dysfunction in diabetic mice. Furthermore, mitophagy could not be activated and induced by HIF-1α agonist DMOG in Park2−/− diabetic mice. In this study, we first demonstrated that HIF-1α could upregulate mitophagy in the spinal cord of mice with DNP through modulating the Parkin signaling pathway, promoting new insights into the mechanisms and research of treatment strategies for patients with DNP.
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DOI：
10.1038/nrneurol.2014.77
发表时间：
2014-06
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Bennett GJ;Doyle T;Salvemini D
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
6.1
作者：
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通讯作者：
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