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Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes
Joint Authors
Chen, Christine
Loughran, Patricia
Billiar, Timothy R.
Sun, Qian
Scott, Melanie J.
Deng, Meihong
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-02-10
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Impairment of autophagy has been associated with liver injury.
TLR4-stimulation by LPS upregulates autophagy in hepatocytes, although the signaling pathways involved remain elusive.
The objective of this study was to determine the signaling pathway leading to LPS-stimulated autophagy in hepatocytes.
Cell lysates from livers of wild type (WT; C57BL/6) mice given LPS (5 mg/kg-IP) and hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to 24 h were collected.
LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined by immunoblot, immunofluorescence, and qPCR.
Autophagy-like activation was measured by GFP-LC3-puncta formation and LC3II-expression.
Beclin1, Nrf2, p62, MyD88, and TIRAP were knocked-down using siRNA.
LC3II-expression increased in both liver and hepatocytes after LPS and was dependent on TLR4.
Beclin1 expression did not increase after LPS in hepatocytes and beclin1-knockdown did not affect LC3II levels.
In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3.
p62-knockdown prevented LC3II puncta formation.
LPS-induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of both Nrf2 and NFκB transcription factors to the nucleus to upregulate p62-expression.
Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1-mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress.
American Psychological Association (APA)
Chen, Christine& Deng, Meihong& Sun, Qian& Loughran, Patricia& Billiar, Timothy R.& Scott, Melanie J.. 2014. Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes. BioMed Research International،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-458820
Modern Language Association (MLA)
Chen, Christine…[et al.]. Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes. BioMed Research International No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-458820
American Medical Association (AMA)
Chen, Christine& Deng, Meihong& Sun, Qian& Loughran, Patricia& Billiar, Timothy R.& Scott, Melanie J.. Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-458820
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-458820