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J. Venom. Anim. Toxins incl. Trop. Dis. Original paper - ISSN 1678-9199. |
Action of neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi venom, on skeletal muscle: an ultrastructural and immunocytochemistry study
Baldo C (1), Ferreira MJ (2), Lopes DS (2), Izidoro LFM (3), Gomes AO (4), Ferro EAV (4), Hamaguchi A (5), Homsi-Brandeburgo MI (5), Rodrigues (5) VM
(1) Laboratory of Immunopathology, Butantan Institute, São Paulo, São Paulo State, Brazil (2) Special Laboratory of Applied Toxinology, CAT/CEPID, Butantan Institute, São Paulo, São Paulo State, Brazil; (3) Integrated Sciences School of Pontal&endash;Federal University of Uberlândia; (4) Institute of Biomedical Science, Federal University of Uberlândia, Uberlândia, Minas Gerais State, Brazil; (5), Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais State, Brazil.
ABSTRACT: The damaging effects of neuwiedase, a non-hemorrhagic snake venom metalloproteinase from P-I class, on gastrocnemius muscle are reported in this study. Ultrastructural alterations after neuwiedase injection were detected early, showing disarrangement of skeletal muscle fibers characterized by discontinuity of Z lines, mitochondrial swelling and disruption of plasma membrane and basal lamina. Degradation of skeletal muscle fibers and appearance of an amorphous substance, primarily composed of cellular debris, were noted after 24 hours. The presence of neuwiedase at the injection site (detected by immunocytochemistry) revealed highly specific labeling of myofibril components of damaged myocytes. In addition, proteolysis of muscle proteins assayed by using myofibrils extracted from gastrocnemius muscle indicated that neuwiedase provoked degradation of myofibrils, especially myosin. These results suggest that skeletal muscle damage induced by neuwiedase is probably due to its proteolytic action on myofibrils, which are responsible for the maintenance of the cellular architecture.
KEY WORDS: skeletal muscle, neuwiedase, snake venom metalloproteinases, Bothrops neuwiedi.