Differential transcript profile of inhibitors with potential anti-venom role in the liver of juvenile and adultBothrops jararacasnake

Author:

Gomes Cícera Maria12,Morais-Zani Karen de12,Lu Stephen3,Buarque Diego de Souza3,Braz Glória Regina Cardoso45,Grego Kathleen Fernandes1,Tanaka Aparecida Sadae56,Tanaka-Azevedo Anita Mitico12

Affiliation:

1. Laboratório de Herpetologia, Instituto Butantan, São Paulo, Brazil

2. Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, Brazil

3. Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, Brazil

4. Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

5. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, São Paulo, Brazil

6. Escola Paulista de Medicina / Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, Brazil

Abstract

BackgroundSnakes belonging to theBothropsgenus are vastly distributed in Central and South America and are responsible for most cases of reported snake bites in Latin America. The clinical manifestations of the envenomation caused by this genus are due to three major activities—proteolytic, hemorrhagic and coagulant—mediated by metalloproteinases, serine proteinases, phospholipases A2and other toxic compounds present in snake venom. Interestingly, it was observed that snakes are resistant to the toxic effects of its own and other snake’s venoms. This natural immunity may occur due the absence of toxin target or the presence of molecules in the snake plasma able to neutralize such toxins.MethodsIn order to identify anti-venom molecules, we construct a cDNA library from the liver ofB. jararacasnakes. Moreover, we analyzed the expression profile of four molecules—the already known anti-hemorrhagic factor Bj46a, one gamma-phospholipase A2inhibitor, one inter-alpha inhibitor and one C1 plasma protease inhibitor—in the liver of juvenile and adult snakes by qPCR.ResultsThe results revealed a 30-fold increase of gamma-phospholipase A2inhibitor and a minor increase of the inter-alpha inhibitor (5-fold) and of the C1 inhibitor (3-fold) in adults. However, the Bj46a factor seems to be equally transcribed in adults and juveniles.DiscussionThe results suggest the up-regulation of different inhibitors observed in the adult snakes might be a physiological adaptation to the recurrent contact with their own and even other snake’s venoms throughout its lifespan. This is the first comparative analysis of ontogenetic variation of expression profiles of plasmatic proteins with potential anti-venom activities of the venomous snakeB. jararaca. Furthermore, the present data contributes to the understanding of the natural resistance described in these snakes.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Tecnológico (CNPq)

INCT—Entomologia Molecular

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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