Hydrogen alleviates cell damage and acute lung injury in sepsis via PINK1/Parkin-mediated mitophagy

Hongguang Chen, Huaying Lin, Beibei Dong, Yaoqi Wang, Yonghao Yu, Keliang Xie

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DOI: 10.1007/s00011-021-01481-y DOI is the universal ID for this study.

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Abstract:

Background: Multiple organ failure (MOF) is the main cause of early death in septic shock. Lungs are among the organs that are affected in MOF, resulting in acute lung injury. Inflammation is an important factor that causes immune cell dysfunction in the pathogenesis of sepsis. Autophagy is involved in the process of inflammation and also occurs in response to cell and tissue injury in several diseases. We previously demonstrated that hydrogen alleviated the inflammation-induced cell injury and organ damage in septic mice. Aim: The focus of the present study was to elucidate whether mitophagy mediates the inflammatory response or oxidative injury in sepsis in vitro and in vivo. Furthermore, we evaluated the role of mitophagy in the protective effects of hydrogen against cell injury or organ dysfunction in sepsis. Method: RAW 264.7 macrophages induced by lipopolysaccharide (LPS) were used as an in vitro model for inflammation, and cecal ligation and puncture (CLP)-induced acute lung injury mice were used as an in vivo model for sepsis. The key protein associated with mitophagy, PTEN-induced putative kinase 1 (PINK1), was knocked down by PINK1 shRNA transfection in RAW 264.7 macrophages or mice.

Results: Hydrogen ameliorated cell injury and enhanced mitophagy in macrophages stimulated by LPS. PINK1 was required for the mitigation of the cell impairment in LPS-stimulated macrophages by hydrogen treatment. PINK1 knockdown abrogated the beneficial effects of hydrogen on mitophagy in LPS-stimulated macrophages. Hydrogen inhibited acute lung injury in CLP mice via activation of PINK1-mediated mitophagy.

Conclusion: These results suggest that PINK1-mediated mitophagy plays a key role in the protective effects of hydrogen against cell injury in LPS-induced inflammation and CLP-induced acute lung injury.


Publish Year 2021
Country China
Rank Positive
Journal Inflammation Research
Primary Topic Lung
Secondary Topic Sepsis
Model Cell Culture
Tertiary Topic Multiple Organ Dysfunction Syndrome (MODS)
Vehicle Medium (Dissolved)
pH Neutral
Application Culture Media
Comparison
Complement