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

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 221, JUN 15 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/17943-6 - Proteomic and peptidomic analysis of snake venom effect on cancer cell lines and mouse brain tissues
• Grantee: Leo Kei Iwai
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
• Grantee: Emer Suavinho Ferro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 17/06496-9 - Proteomic characterization of the effect of Bothrops jararaca snake venom on normal vs cancer cell lines
• Grantee: Carolina Yukiko Kisaki
• Support Opportunities: Scholarships in Brazil - Master