HIF-1 alpha Ameliorates Diabetic Neuropathic Pain via Parkin-Mediated Mitophagy in a Mouse Model

BioMed research international(2022)

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摘要
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 1 alpha subunit (HIF-1 alpha) plays a vital role in mitochondrial homeostasis under hypoxia. However, it remains unclear whether mitophagy was changed and could be regulated by HIF-1 alpha in DNP. In this study, the results showed that mitophagy was activated and HIF-1 alpha was upregulated in the spinal cord of diabetic mice. HIF-1 alpha agonist dimethyloxalylglycine (DMOG) could further elevate HIF-1 alpha 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-1 alpha agonist DMOG in Park2(-/-) diabetic mice. In this study, we first demonstrated that HIF-1 alpha 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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关键词
diabetic neuropathic pain,mitophagy,parkin-mediated
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