1. Brucella infection inhibits macrophages apoptosis via Nedd4-dependent degradation of calpain2.
- Author
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Cui G, Wei P, Zhao Y, Guan Z, Yang L, Sun W, Wang S, and Peng Q
- Subjects
- Analysis of Variance, Animals, Apoptosis genetics, Blotting, Western, Brucella genetics, Calpain metabolism, Cell Line, Densitometry, Electrophoresis, Polyacrylamide Gel, Humans, Immunoprecipitation, In Situ Nick-End Labeling, Macrophages physiology, Mice, Microscopy, Fluorescence, Nedd4 Ubiquitin Protein Ligases, RNA Interference, Ubiquitination, Apoptosis physiology, Brucella pathogenicity, Brucellosis immunology, Endosomal Sorting Complexes Required for Transport metabolism, Gene Expression Regulation physiology, Macrophages microbiology, Ubiquitin-Protein Ligases metabolism
- Abstract
The calcium-dependent protease calpain2 is involved in macrophages apoptosis. Brucella infection-induced up-regulation of intracellular calcium level is an essential factor for the intracellular survival of Brucella within macrophages. Here, we hypothesize that calcium-dependent E3 ubiquitin ligase Nedd4 ubiquitinates calpain2 and inhibits Brucella infection-induced macrophage apoptosis via degradation of calpain2.Our results reveal that Brucella infection induces increases in Nedd4 activity in an intracellular calcium dependent manner. Furthermore, Brucella infection-induced degradation of calpain2 is mediated by Nedd4 ubiquitination of calpain2. Brucella infection-induced calpain2 degradation inhibited macrophages apoptosis. Treatment of Brucella infected macrophages with calcium chelator BAPTA or Nedd4 knock-down decreased Nedd4 activity, prevented calpain2 degradation, and resulted in macrophages apoptosis., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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