title: Brucella infection inhibits macrophages apoptosis via Nedd4-dependent degradation of calpain2.
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.
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Guimei
authors.initials: G
authors.lastname: Cui
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wei
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Wanchun
authors.initials: W
authors.lastname: Sun
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan City 250012, Shandong, China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China. Electronic address: Qishengpeng@yahoo.com.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Peng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002002:Brucella / Q000235:genetics / Q000472:pathogenicity*; D002006:Brucellosis / Q000276:immunology*; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D000075702:Nedd4 Ubiquitin Protein Ligases; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases; D002154:Calpain
keywords: Apoptosis; Brucella abortus; Calpain2; Intracellular calcium; Nedd4