HO-1PINK1 Regulated Mitochondrial FusionFission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury
Joint Authors
Sun, Yi
Shi, Jia
Li, Hai-Bo
Zhang, Xi-Zhe
Song, Jian-Nan
Hu, Zhan-Fei
Wu, Jian-Nan
Yu, Jian-Bo
Zhou, Qi
Li, Yun
Guo, Ying
Zhang, Yuan
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-10-22
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Background.
Endotoxin-associated acute kidney injury (AKI), a disease characterized by marked oxidative stress and inflammation disease, is a major cause of mortality in critically ill patients.
Mitochondrial fission and pyroptosis often occur in AKI.
However, the underlying biological pathways involved in endotoxin AKI remain poorly understood, especially those related to mitochondrial dynamics equilibrium disregulation and pyroptosis.
Previous studies suggest that heme oxygenase- (HO-) 1 confers cytoprotection against AKI during endotoxic shock, and PTEN-induced putative kinase 1 (PINK1) takes part in mitochondrial dysfunction.
Thus, in this study, we examine the roles of HO-1/PINK1 in maintaining the dynamic process of mitochondrial fusion/fission to inhibit pyroptosis and mitigate acute kidney injury in rats exposed to endotoxin.
Methods.
An endotoxin-associated AKI model induced by lipopolysaccharide (LPS) was used in our study.
Wild-type (WT) rats and PINK1 knockout (PINK1KO) rats, respectively, were divided into four groups: the control, LPS, Znpp+LPS, and Hemin+LPS groups.
Rats were sacrificed 6 h after intraperitoneal injecting LPS to assess renal function, oxidative stress, and inflammation by plasma.
Mitochondrial dynamics, morphology, and pyroptosis were evaluated by histological examinations.
Results.
In the rats with LPS-induced endotoxemia, the expression of HO-1 and PINK1 were upregulated at both mRNA and protein levels.
These rats also exhibited inflammatory response, oxidative stress, mitochondrial fission, pyroptosis, and decreased renal function.
After upregulating HO-1 in normal rats, pyroptosis was inhibited; mitochondrial fission and inflammatory response to oxidative stress were decreased; and the renal function was improved.
The effects were reversed by adding Znpp (a type of HO-1 inhibitor).
Finally, after PINK1 knockout, there is no statistical difference in the LPS-treated group and Hemin or Znpp pretreated group.
Conclusions.
HO-1 inhibits inflammation response and oxidative stress and regulates mitochondria fusion/fission to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.
American Psychological Association (APA)
Li, Hai-Bo& Zhang, Xi-Zhe& Sun, Yi& Zhou, Qi& Song, Jian-Nan& Hu, Zhan-Fei…[et al.]. 2020. HO-1PINK1 Regulated Mitochondrial FusionFission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury. BioMed Research International،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1132370
Modern Language Association (MLA)
Li, Hai-Bo…[et al.]. HO-1PINK1 Regulated Mitochondrial FusionFission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury. BioMed Research International No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1132370
American Medical Association (AMA)
Li, Hai-Bo& Zhang, Xi-Zhe& Sun, Yi& Zhou, Qi& Song, Jian-Nan& Hu, Zhan-Fei…[et al.]. HO-1PINK1 Regulated Mitochondrial FusionFission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1132370
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1132370