Daboia russelli Venom Hyaluronidase: Purification, Characterization and Inhibition by beta-3-(3-Hydroxy-4-Oxopyridyl) alpha-Amino-Propionic Acid

Mahadeswaraswamy, Y. H. and Manjula, B. and Devaraja, S. and Girish, K. S. and Kemparaju, K. (2011) Daboia russelli Venom Hyaluronidase: Purification, Characterization and Inhibition by beta-3-(3-Hydroxy-4-Oxopyridyl) alpha-Amino-Propionic Acid. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 11 (20). pp. 2556-2565.

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Official URL: http://dx.doi.org/10.2174/156802611797633410

Abstract

The present study describes the purification and characterization of a hyaluronidase (DRHyal-II) from Daboia/Vipera russelli venom and its inhibition by beta-3-(3-hydroxy-4-oxopyridyl) alpha-amino-propionic acid, the mimosine. Gel permeation and ion exchange chromatography were employed to isolate DRHyal-II. The molecular mass by MALDI-TOF mass spectrometry was found to be 28.3 kDa. Single band in reduced SDS-PAGE suggested the monomeric nature. It was optimally active at pH 5.5 and at 37 degrees C and require 150 mM NaCl in the reaction mixture. It was specific to hyaluronan substrate and belongs to class-I or the neutral active enzymes. DRHyal-II was non-toxic by itself but, it potentiated the myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of hemorrhagic complex (HC). In in vitro experiments, mimosine inhibited the activity of DRHyal-II and the hyaluronidase activity of whole venom dose dependently. In in vivo experiments, mimosine inhibited the DRHyal-II potentiated myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of HC. The inhibition was due to the formation of DRHyal-II-mimosine inhibitory complex that resulted in significant structural changes at secondary and tertiary levels as evidenced by fluorescence emission and CD spectral studies. Hence, in this study an attempt was made to establish the possible role of hyaluronidase activity in the pathology of Daboia/Vipera russelli venom and the beneficial effects of its inhibition with special emphasis on the management of local toxicity.

Item Type: Article
Uncontrolled Keywords: Hyaluronidase; spreading factor; extracellular matrix; hyaluronan; mimosine; local toxicity; snakebite
Subjects: Agriculture Biological Sciences > Biochemistry
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biochemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Biochemistry
Depositing User: Users 1 not found.
Date Deposited: 15 Mar 2013 11:53
Last Modified: 09 May 2013 04:31
URI: http://eprints.uni-mysore.ac.in/id/eprint/1968

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