title: Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.
abstract: The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM) and other extracellular matrix (ECM) proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs) or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.
authors.affiliation: Facultad de Farmacia, Universidad de Costa Rica, San José, Costa Rica.|Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Cristina
authors.initials: C
authors.lastname: Herrera
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Jéssica Kele A
authors.initials: JK
authors.lastname: Macêdo
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Andrés
authors.initials: A
authors.lastname: Feoli
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Teresa
authors.initials: T
authors.lastname: Escalante
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rucavado
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Fox
mesh_terms: D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D006651:Histocytochemistry; D007150:Immunohistochemistry; D051379:Mice; D009132:Muscles / Q000737:chemistry / Q000473:pathology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D013997:Time Factors
chemical_list: D003435:Crotalid Venoms; D020543:Proteome