Proteomic analysis reveals rattlesnake venom modulation of proteins associated with cardiac tissue damage in mouse hearts

Author(s):Show less -

Santos, W. S. ; Montoni, Fabio ; Eichler, R. A. S. ; Suehiro Arcos, Stephanie Santos ; Andreotti, Diana Zukas ; Kisaki, Carolina Yukiko ; Evangelista, Kimberly Borges ; Calacina, Hamida Macedo ; Lima, Ismael Feitosa ; Maltauro Soares, Magna Aparecida ; Kyle Gren, Eric Conrad ; Carvalho, Valdemir Melechco ; Ferro, Emer Suavinho ; Nishiyama-Jr, Milton Yutaka ; Chen, Zhibin ; Iwai, Leo Kei

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 258, p. 12-pg., 2022-04-30.

Abstract

Snake envenomation is a common but neglected disease that affects millions of people around the world annually. Among venomous snake species in Brazil, the tropical rattlesnake (Crotalus durissus terrificus) accounts for the highest number of fatal envenomations and is responsible for the second highest number of bites. Snake venoms are complex secretions which, upon injection, trigger diverse physiological effects that can cause significant injury or death. The components of C. d. terrificus venom exhibit neurotoxic, myotoxic, hemotoxic, nephrotoxic, and cardiotoxic properties which present clinically as alteration of central nervous system function, motor paralysis, seizures, eyelid ptosis, ophthalmoplesia, blurred vision, coagulation disorders, rhabdomyolysis, myoglobinuria, and cardiorespiratory arrest. In this study, we focused on proteomic characterization of the cardiotoxic effects of C. d. terrificus venom in mouse models. We injected venom at half the lethal dose (LD50) into the gastrocnemius muscle. Mouse hearts were removed at set time points after venom injection (1 h, 6 h, 12 h, or 24 h) and subjected to trypsin digestion prior to high-resolution mass spectrometry. We analyzed the proteomic profiles of >1300 proteins and observed that several proteins showed noteworthy changes in their quantitative profiles, likely reflecting the toxic activity of venom components. Among the affected proteins were several associated with cellular deregulation and tissue damage. Changes in heart protein abundance offer insights into how they may work synergistically upon envenomation. Significance: Venom of the tropical rattlesnake (Crotalus durissus terririficus) is known to be neurotoxic, myotoxic, nephrotoxic and cardiotoxic. Although there are several studies describing the biochemical effects of this venom, no work has yet described its proteomic effects in the cardiac tissue of mice. In this work, we describe the changes in several mouse cardiac proteins upon venom treatment. Our data shed new light on the clinical outcome of the envenomation by C. d. terrificus, as well as candidate proteins that could be investigated in efforts to improve current treatment approaches or in the development of novel therapeutic interventions in order to reduce mortality and morbidity resulting from envenomation. (AU)

• 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
• 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: 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: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
• Grantee: Emer Suavinho Ferro
• Support Opportunities: Research Projects - Thematic Grants