Okinalysin, a Novel P-I Metalloproteinase from Ovophis okinavensis: Biological Properties and Effect on Vascular Endothelial Cells

Toxins

Yumiko Komori¹  Eri Murakami¹  Kei-ichi Uchiya¹  Tunemasa Nonogaki² 

[1] Department of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan; E-Mails:;College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya 463-8521, Japan; E-Mail:

关键词: Ovophis okinavensis venom;    hemorrhagic toxin;    metalloproteinase;    vascular endothelial cell;    cytotoxicity;   

DOI  :  10.3390/toxins6092594

来源: mdpi

【 摘 要 】

A novel hemorrhagic metalloproteinase, okinalysin, was isolated from the venom of Ovophis okinavensis. It possessed caseinolytic and hemorrhagic activities, and also hydrolyzed fibrinogen and collagen. These activities were inhibited by ethylenediaminetetraacetic acid (EDTA) but not by p-amidinophenyl methanesulfonyl fluoride hydrochloride (APMSF). The molecular mass of okinalysin was 22,202 Da measured by MALDI/TOF mass spectrometry. The primary structure of okinalysin was partially determined by Edman sequencing, and the putative zinc-binding domain HEXXHXXGXXH was found to be present in its structure. From these data, okinalysin is defined as a metalloproteinase belonging to a P-I class. The partial amino acid sequence of okinalysin was homologous to the C-terminus of MP 10, a putative metalloproteinase induced from transcriptome of the venom gland cDNA sequencing of O. okinavensis. Okinalysin possessed cytotoxic activity on cultured endothelial cells, and the EC₅₀ on human pulmonary artery endothelial cells was determined to be 0.6 μg/mL. The histopathological study also showed that okinalysin causes the leakage of red blood cells and neutrophil infiltration. These results indicate that destruction of blood vessels by okinalysin is one of the main causes of hemorrhage.

【 授权许可】

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