VvpM, an Extracellular Metalloprotease of Vibrio vulnificus, Induces Apoptotic Death of Human Cells

Mi-Ae Lee; Jeong-A Kim; Yu Jin Yang; Mee-Young Shin; Soon-Jung Park; Kyu-Ho Lee

doi:10.1007/s12275-014-4531-0

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VvpM, an Extracellular Metalloprotease of Vibrio vulnificus, Induces Apoptotic Death of Human Cells: Mi-Ae Lee ¹, Jeong-A Kim ¹, Yu Jin Yang ², Mee-Young Shin ², Soon-Jung Park ², Kyu-Ho Lee ¹; Journal of Microbiology 2014;52(12):1036-1043.
DOI: https://doi.org/10.1007/s12275-014-4531-0
Published online: November 3, 2014

¹Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea, ²Department of Environmental Medical Biology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea¹Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea, ²Department of Environmental Medical Biology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea

Corresponding author: Kyu-Ho Lee , Tel: +82-2-705-7963,

Received: 24 September 2014 • Revised: 10 October 2014 • Accepted: 14 October 2014

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Abstract

A pathogenic bacterium, Vibrio vulnificus produces various extracellular proteases including the elastolytic metalloprotease, VvpE. In silico analysis of its genome revealed a VvpEhomologous 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.

Keywords: metalloprotease;apoptosis;Vibrio vulnificus

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VvpM, an Extracellular Metalloprotease of Vibrio vulnificus, Induces Apoptotic Death of Human Cells

J. Microbiol. 2014;52(12):1036-1043. Published online November 3, 2014

DOI: https://doi.org/10.1007/s12275-014-4531-0

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