Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5800562 | Veterinary Microbiology | 2014 | 11 Pages |
â¢Brucella infection enhances calcium-dependent activity of Nedd4 E3 ligase.â¢Brucella infection decreases the calpain activity via degradation of calpain2 protein.â¢Nedd4 E3 ligase activity is required for calpain2 degradation in B. abortus-infected macrophages.â¢Brucella infection inhibits Nedd4 activation-dependent macrophages apoptosis via degradation of calpain2.
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.