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p62 is involved in the mechanism of Mallory body formation
Li Nan1, Yong Wu, Fawzia Bardag-Gorce
1Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Abstract:
p62 is a scaffolding protein that binds to polyubiquitin. It is involved in the degradation of proteins by the proteasome. To determine if p62 is critical in the development of Mallory bodies (MBs), primary culture hepatocytes from drug-primed mice were studied and the results were compared with normal hepatocytes. Gene-specific gripNA (gp62) was added to the medium of the primary cultures of the hepatocytes to inhibit the expression of p62. Overexpression of p62 was achieved by transfecting the hepatocytes with a plasmid containing green fluorescent protein (GFP) fused p62 (p62-GFP). Gp62 dramatically inhibited MB formation by 94% in drug-primed hepatocytes. The cells transfected with gp62 had decreased protein levels of p62, ubiquitin (Ub), and cytokeratin 8 (CK8). Overexpression of p62 accelerated and enhanced MB formation by 339% in drug-primed hepatocytes. Overexpression of p62 in normal mouse hepatocytes induced MB-like aggresomes that were stained by Ub but not by CK8. The results indicate that p62 is involved in the mechanism of MB formation.
Insights
p62 protein is crucial for Mallory body formation in liver cells. Inhibiting p62 significantly reduced Mallory body development, while overexpressing it accelerated their formation.
Area of Science:
- Hepatology
- Cell Biology
- Protein Degradation
Background:
- p62 is a scaffolding protein that binds polyubiquitin and participates in proteasomal degradation.
- Mallory bodies (MBs) are protein aggregates found in hepatocytes, implicated in liver injury.
Purpose of the Study:
- To investigate the role of p62 in the formation of Mallory bodies (MBs).
Main Methods:
- Primary mouse hepatocytes were cultured and treated with drug-priming.
- p62 expression was inhibited using gene-specific gripNA (gp62).
- p62 overexpression was achieved via transfection with p62-green fluorescent protein (GFP) plasmid.
Main Results:
- gp62 treatment inhibited MB formation by 94% in drug-primed hepatocytes, decreasing levels of p62, ubiquitin (Ub), and cytokeratin 8 (CK8).
- Overexpression of p62 enhanced MB formation by 339% in drug-primed hepatocytes.
- p62 overexpression in normal hepatocytes induced Ub-positive, CK8-negative MB-like aggresomes.
Conclusions:
- p62 plays a critical role in the mechanism of Mallory body formation.
- Modulating p62 levels affects the development of hepatic protein aggregates.
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