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The impact of rattlesnake venom on mice cerebellum proteomics points to synaptic inhibition and tissue damage

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Autor(es):
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Montoni, Fabio [1, 2] ; Andreotti, Diana Zukas [3] ; dos Santos Eichler, Rosangela Aparecida [3] ; Santos, Wellington da Silva [1, 2] ; Kisaki, Carolina Yukiko [1, 2] ; Suehiro Arcos, Stephanie Santos [1, 2] ; Lima, Ismael Feitosa [1, 2] ; Maltauro Soares, Magna Aparecida [4] ; Nishiyama-Jr, Milton Yutaka ; Nava-Rodrigues, Daniel [5] ; Ferro, Emer Suavinho [3] ; Carvalho, Valdemir Melechco [6] ; Iwai, Leo Kei [7, 8]
Número total de Autores: 13
Afiliação do(s) autor(es):
[1] Butantan Inst, LETA CeTICS, Lab Appl Toxinol, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[2] Butantan Inst, LETA CeTICS, Ctr Toxins Immune Response & Cell Signaling, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Biomed Sci Inst ICB, Dept Pharmacol, Av Prof Lineu Prestes 1524, Sala 317, BR-05508000 Sao Paulo, SP - Brazil
[4] Butantan Inst, Lab Pathophysiol, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[5] Royal Marsden NHS Fdn Trust, Inst Canc Res, 15 Cotswold Rd, London SM2 5NG - England
[6] Grp Fleury, Av Joao Pedro Cardoso 158, BR-04355000 Sao Paulo, SP - Brazil
[7] Nishiyama-Jr, Jr., Milton Yutaka, Butantan Inst, LETA CeTICS, Lab Appl Toxinol, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[8] Nishiyama-Jr, Jr., Milton Yutaka, Butantan Inst, LETA CeTICS, Ctr Toxins Immune Response & Cell Signaling, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PROTEOMICS; v. 221, JUN 15 2020.
Citações Web of Science: 0
Resumo

Snake envenomation is responsible for more than 130,000 deaths worldwide. In Brazil, the Crotalus rattlesnake is responsible for the second largest number of accidental snake bites in the country. Although there are many descriptions of the clinical and biochemical effects of Crotalus envenoming, there are few works describing the molecular events in the central nervous system of an organism due to envenomation. In this study, we analyzed the proteomic effect of Crotalus durissus terrificus snake venom on mice cerebellums. To monitor the envenomation over time, changes in the protein abundance were evaluated at 1 h, 6 h, 12 h and 24 h after venom injection by mass spectrometry. The analysis of the variation of over 4600 identified proteins over time showed a reduction in components of inhibitory synapse signaling, oxidative stress, and maintenance of neuronal cells, which paralleled increasing tissue damage and apoptosis factors. These analyses revealed the potential protein targets of the C. d terrificus venom on the murine cerebellum, showing new aspects of the snake envenomation effect. These data may contribute to new therapeutic approaches (i.e., approaches directed at protein targets affected by the envenomation) on the treatment of envenomation by the neurotoxic C. d terrificus snake venom. Significance: Snakebites are a neglected global health problem that affects mostly rural and tropical areas of developing countries. It is estimated that over 5.4 million people are bitten by snakes each year, from which 2.7 million people are bitten by venomous snakes, resulting in disabilities such as amputations and in some cases leading to death. The C. d. terrificus snake is the most lethal snake in Brazil. Studying the molecular changes upon envenomation in a specific tissue may lead to a better understanding of the envenomation process by C. d. terrificus snakebites. (AU)

Processo FAPESP: 17/17943-6 - Análise proteômica e peptidômica do efeito da peçonha de serpentes sobre linhagens celulares de câncer e tecidos cerebrais de camundongos
Beneficiário:Leo Kei Iwai
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
Beneficiário:Hugo Aguirre Armelin
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 16/04000-3 - Farmacologia de oligopeptidases e peptídeos intracelulares
Beneficiário:Emer Suavinho Ferro
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
Beneficiário:Ana Marisa Chudzinski-Tavassi
Linha de fomento: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
Processo FAPESP: 17/06496-9 - Caracterização proteômica do efeito da peçonha de Bothrops jararaca sobre linhagens celulares de câncer versus linhagens celulares normais
Beneficiário:Carolina Yukiko Kisaki
Linha de fomento: Bolsas no Brasil - Mestrado