HDAC6 promotes sepsis development by impairing PHB1-mediated mitochondrial respiratory chain function
| Autor: | Jian-Ping Yang, Lichao Sun, Yao Yao, Liu-Wei Zhang, Hong Zhou, Mei-Jia Shen, Hongbo Zhang, Shi-Dong Guo, Shengtao Yan, Wen Li |
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| Rok vydání: | 2020 |
| Předmět: |
Male
China Aging Blotting Western Cell Respiration Rat model PHB1 Pharmacology Histone Deacetylase 6 medicine.disease_cause Rats Sprague-Dawley Sepsis Prohibitins Animals Humans oxidative stress Medicine Prohibitin Cecum Ligation Aged business.industry Cell Biology Middle Aged HDAC6 medicine.disease Mitochondria Rats Repressor Proteins Blot Disease Models Animal Mitochondrial respiratory chain CLP-induced sepsis Case-Control Studies mitochondrial respiratory control rate Female business Oxidative stress Function (biology) Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.102964 |
| Popis: | Objective This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis. Results HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury. Conclusions In this sepsis model, HDAC6 inhibits the expression and function of PHB1 and alters the function of the mitochondrial respiratory chain mediated by PHB1, thus enhancing the production of oxidants and increasing oxidative stress and thereby leading to severe oxidative injury in multiple organs. Methods The expression of HDAC6 and prohibitin 1 (PHB1) in humans and in a rat model of sepsis was measured by quantitative reverse-transcription PCR and western blotting. Sepsis induction by cecal ligation and puncture (CLP) was confirmed by histological analysis. Concentrations of different sepsis markers were measured by an enzyme-linked immunosorbent assay, and mitochondrial function was assessed via the mitochondrial respiratory control rate. |
| Databáze: | OpenAIRE |
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