Journal
VETERINARY MICROBIOLOGY
Volume 174, Issue 1-2, Pages 195-205Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.vetmic.2014.08.033
Keywords
Brucella abortus; Apoptosis; Nedd4; Calpain2; Intracellular calcium
Categories
Funding
- National Natural Science Foundation of China [31372409]
- Jilin University
- National 973 Basic Research Program of China [2013CB530700]
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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. (C) 2014 Elsevier B.V. All rights reserved.
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