Patagonfibrase modifies protein expression of tissue factor and protein disulfide isomerase in rat skin

Author(s)

Elisa Peichoto, Maria ; Santoro, Marcelo Larami

• Document type: Journal article
• Source: Toxicon; v. 119, p. 330-335, SEP 1 2016.
• Web of Science Citations: 4

Abstract

Patagonfibrase is a hemorrhagic metalloproteinase isolated from the venom of the South American rear fanged snake Philodryas patagoniensis, and is an important contributor to local lesions inflicted by this species. The tissue factor (TF)-factor Vila complex, besides triggering the coagulation cascade, has been demonstrated to be involved in inflammatory events. Our aim was to determine whether patagonfibrase affects the expression of TF and protein disulfide isomerase (PDI), an enzyme that controls TF biological activity, at the site of patagonfibrase injection, and thus if they may play a role in hemostatic and inflammatory events induced by snake venoms. Patagonfibrase (60 mu g/kg) was administered s.c. to rats, and after 3 h blood was collected to evaluate hemostasis parameters, and skin fragments close to the site of injection were taken to assess TF and PDI expression. Patagonfibrase did not alter blood cell counts, plasma fibrinogen levels, or levels of TF activity in plasma. However, by semiquantitative Western blotting, patagonfibrase increased TF expression by 2-fold, and decreased PDI expression by 3-fold in skin samples. In agreement, by immunohistochemical analyses, prominent TF expression was observed in the subcutaneous tissue. Thus, patagonfibrase affects the local expression of TF and PDI without inducing any systemic hemostatic disturbance, although that they may be involved in the local inflammatory events induced by hemorrhagic metalloproteinases. Once antivenom therapy is not totally effective to treat the local injury induced by snake venoms, modulation of the activity and expression of TF and/or PDI might become a strategy for treating snake envenomation. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 10/08162-1 - Contribution of local injury evoked by Bothrops jararaca snake venom to the genesis of systemic hemostatic disturbances
• Grantee: Marcelo Larami Santoro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/52559-3 - Importance of local damage induced by snake venom metalloproteinases in the induction of thrombocytopenia in envenomations
• Grantee: Marcelo Larami Santoro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/25177-0 - Involvement of Von Willebrand factor in hemostatic disturbances induced by Bothrops jararaca snake venom: experimental study
• Grantee: Marcelo Larami Santoro
• Support Opportunities: Regular Research Grants