Isolation and characterization of a myotoxin from the venom of Macrovipera lebetina transmediterranea.
The Macrovipera lebetina venom consists of a complex mixture of proteins belonging to a few main families according to their enzymatic and pharmacological activity. Given the serious pathophysiological effects caused by M. lebetina bites mainly induced by muscle degeneration, we decided to investigate the myotoxic activity of some venom fractions. In the present study we describe the purification and characterization of a 22.600 kDa protein, named in the following Mlp4.2, that shares myotoxic but not haemorrhagic activity in vivo. Herein we report that Mlp4.2 is a metalloproteinase belonging to the PI-SVMPS family able, in vitro, to proteolyse extracellular matrix proteins as laminin and fibronectin. Histological observations of mouse anterior tibialis Mlp4.2-treated muscle, demonstrate that this protein induces a massive degeneration of myofibers but not haemorrhage. The immunofluorescence analysis of protein-treated anterior tibialis, demonstrates that Mlp4.2 is able to disarray the laminin network surrounding muscle fibers. Finally Mlp4.2 did not show any direct cytolytic activity towards the myogenic cell line C2C12 in culture. The data reported herein suggest that the myotoxicity of Mlp4.2 is primarily linked to the disruption of the muscle fibers interaction with extracellular matrix proteins.
Hamza
Loubna
L
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédienne Bab Ezzouar, Alger, Algeria.
Girardi
Tiziana
T
Castelli
Silvia
S
Gargioli
Cesare
C
Cannata
Stefano
S
Patamia
Maria
M
Luly
Paolo
P
Laraba-Djebari
Fatima
F
Petruzzelli
Raffaele
R
Rufini
Stefano
S
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization; D014757:Viper Venoms / Q000737:chemistry* / Q000633:toxicity
D014757:Viper Venoms