NDLI: Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes

Content Provider	PubMed Central
Author	Chen, Christine Deng, Meihong Sun, Qian Loughran, Patricia Billiar, Timothy R. Scott, Melanie J.
Copyright Year	2014
Abstract	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 NF κ B 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.
Related Links	http://dx.doi.org/10.1155/2014/267350
Starting Page	267350
File Format	PDF
ISSN	23146133
e-ISSN	23146141
Journal	BioMed Research International
Volume Number	2014
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	2014-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The Role of the Selective Adaptor p62 and Ubiquitin-Like Proteins in Autophagy

Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy

Calpain-dependent clearance of the autophagy protein p62/SQSTM1 is a contributor to ΔPK oncolytic activity in melanoma

p62/SQSTM1-Dependent Autophagy of Lewy Body-Like α-Synuclein Inclusions

Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk

Oligomerization of p62 allows for selection of ubiquitinated cargo andisolation membrane during selective autophagy

To aggregate or not to aggregate? A new role for p62

Toll-like receptors control autophagy

TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS)

Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes

Similar Documents

The Role of the Selective Adaptor p62 and Ubiquitin-Like Proteins in Autophagy

Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy

Calpain-dependent clearance of the autophagy protein p62/SQSTM1 is a contributor to ΔPK oncolytic activity in melanoma

p62/SQSTM1-Dependent Autophagy of Lewy Body-Like α-Synuclein Inclusions

Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk

Oligomerization of p62 allows for selection of ubiquitinated cargo andisolation membrane during selective autophagy

To aggregate or not to aggregate? A new role for p62

Toll-like receptors control autophagy

TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS)

Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes