Research Paper Volume 12, Issue 6 pp 5411—5422
HDAC6 promotes sepsis development by impairing PHB1-mediated mitochondrial respiratory chain function
- 1 Emergency Department of China-Japan Friendship Hospital, Beijing, China
- 2 Surgical Intensive Care Unit of China-Japan Friendship Hospital, Beijing, China
- 3 Department of Emergency, China Emergency General Hospital, Beijing, China
- 4 Department of Physical Constitution and Health, Sport Science College, Beijing Sport University, Beijing, China
Received: June 19, 2019 Accepted: February 19, 2020 Published: March 28, 2020https://doi.org/10.18632/aging.102964
How to Cite
Copyright © 2020 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.