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VvpM, an extracellular metalloprotease of Vibrio vulnificus, induces apoptotic death of human cells

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Title: VvpM, an extracellular metalloprotease of Vibrio vulnificus, induces apoptotic death of human cells
Authors: Kyu-Ho Lee, Mi-Ae Lee, Soon-Jung Park, Yu Jin Yang, Mee-Young Shin, Jeong-A Kim
Contributors: Mi Ae Lee, Jeong A Kim, Yu Jin Yang, Mee Young Shin, Soon Jung Park, Kyu Ho Lee, Park, Soon Jung, Shin, Mee Young
Source: Journal of Microbiology. 52:1036-1043
Publisher Information: The Microbiological Society of Korea, 2014.
Publication Year: 2014
Subject Terms: Cytosol/metabolism, 0301 basic medicine, metalloprotease, Vibrio vulnificus/pathogenicity, Bacterial Proteins/metabolism, Caspase 9/metabolism, Recombinant Proteins/chemistry, Apoptosis, Cytochromes c/metabolism, Cytosol, Annexin A5, Vibrio vulnificus, Recombinant Proteins/metabolism, Microscopy, 0303 health sciences, Metalloproteases/metabolism, Caspase 3, apoptosis, Cytochromes c, Caspase 9, Recombinant Proteins, Mitochondria, 3. Good health, Annexin A5/analysis, Caspase 3/metabolism, HT29 Cells, Signal Transduction, Molecular Sequence Data, Electron, Metalloproteases/isolation & purification, 03 medical and health sciences, Vibrio vulnificus/enzymology, Bacterial Proteins, Microscopy, Electron, Transmission, Bacterial Proteins/chemistry, Mitochondria/metabolism, Transmission, Humans, Computer Simulation, Amino Acid Sequence, Apoptosis*/physiology, Bacterial Proteins/genetics, Metalloproteases/chemistry, HCT116 Cells, Metalloproteases/genetics, Enzyme Activation, Metalloproteases, Sequence Alignment
Description: A pathogenic bacterium, Vibrio vulnificus produces various extracellular proteases including the elastolytic metalloprotease, VvpE. In silico analysis of its genome revealed a VvpE-homologous protease, VvpM whose proteolytic activity was abolished by specific inhibitors against metalloproteases. To investigate whether this newly identified protease has pathogenic role in host interaction in addition to proteolytic role, human cell lines were incubated with recombinant VvpM (rVvpM). rVvpM-challenged cells showed typical morphological changes found in cells under apoptosis. Apoptotic cell death was further evidenced by estimating the Annexin V-stained cells, whose proportions were dependent upon the concentrations of rVvpM treated to human cells. To elucidate the signaling pathway for VvpM-induced apoptosis, three MAPKs were tested if their activation were mediated by rVvpM. ERK1/2 was phosphorylated by treatment of rVvpM and rVvpM-induced cell death was blocked by a specific inhibitor against ERK1/2. In rVvpM-treated cells, the cytosolic levels of cytochrome c were increased in a VvpM concentration-dependent manner, while the levels of cytochrome c in mitochondria were decreased. Cell deaths were accompanied by apparent cleavages of procaspases-9 and -3 to the active caspases-9 and -3, respectively. Therefore, this study demonstrates that an extracellular metalloprotease of V. vulnificus, VvpM induces apoptosis of human cells via a pathway consisting of ERK activation, cytochrome c release, and then activation of caspases-9 and -3.
Document Type: Article
File Description: 1036~1043
Language: English
ISSN: 1976-3794
1225-8873
DOI: 10.1007/s12275-014-4531-0
Access URL: https://pubmed.ncbi.nlm.nih.gov/25363631
https://www.ncbi.nlm.nih.gov/pubmed/25363631
https://pubmed.ncbi.nlm.nih.gov/25363631/
http://dspace.kci.go.kr/handle/kci/108168
https://link.springer.com/article/10.1007/s12275-014-4531-0
Rights: Springer TDM
CC BY NC ND
Accession Number: edsair.doi.dedup.....a9b1b7d2bf42a065cd088c85b6079722
Database: OpenAIRE
Description
Abstract:A pathogenic bacterium, Vibrio vulnificus produces various extracellular proteases including the elastolytic metalloprotease, VvpE. In silico analysis of its genome revealed a VvpE-homologous protease, VvpM whose proteolytic activity was abolished by specific inhibitors against metalloproteases. To investigate whether this newly identified protease has pathogenic role in host interaction in addition to proteolytic role, human cell lines were incubated with recombinant VvpM (rVvpM). rVvpM-challenged cells showed typical morphological changes found in cells under apoptosis. Apoptotic cell death was further evidenced by estimating the Annexin V-stained cells, whose proportions were dependent upon the concentrations of rVvpM treated to human cells. To elucidate the signaling pathway for VvpM-induced apoptosis, three MAPKs were tested if their activation were mediated by rVvpM. ERK1/2 was phosphorylated by treatment of rVvpM and rVvpM-induced cell death was blocked by a specific inhibitor against ERK1/2. In rVvpM-treated cells, the cytosolic levels of cytochrome c were increased in a VvpM concentration-dependent manner, while the levels of cytochrome c in mitochondria were decreased. Cell deaths were accompanied by apparent cleavages of procaspases-9 and -3 to the active caspases-9 and -3, respectively. Therefore, this study demonstrates that an extracellular metalloprotease of V. vulnificus, VvpM induces apoptosis of human cells via a pathway consisting of ERK activation, cytochrome c release, and then activation of caspases-9 and -3.
ISSN:19763794
12258873
DOI:10.1007/s12275-014-4531-0