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

Montoni, Fabio; Andreotti, Diana Zukas; Eichler, Rosangela Aparecida dos Santos; Santos, Wellington da Silva; Kisaki, Carolina Yukiko; Arcos, Stephanie Santos Suehiro; Lima, Ismael Feitosa; Soares, Magna Aparecida Maltauro; Nishiyama-Jr, Milton Yutaka; Nava-Rodrigues, Daniel; Ferro, Emer S.; Carvalho, Valdemir Melechco; Iwai, Leo Kei

doi:10.1016/j.jprot.2020.103779

Cited by 8 publications

(8 citation statements)

References 68 publications

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“…The reaction was stopped by adding 30 μL of 100% acetic acid. Samples volume were reduced in a SpeedVac (Hetovac VR-1, Heto Lab Equipment, Allerød, Denmark) until the volume has lowered to 50 μL and were further desalted on in-house manufactured stop-and-go extraction tips (Stage-Tip) with three SDB-XC (styrene-divinylbenzene, Empore, 3M, Royersford, PA, USA) membranes as previously described [ 147 ]. The stage-tips were initially conditioned with 100% methanol followed by 0.1% formic acid.…”

Section: Methodsmentioning

confidence: 99%

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Kisaki

Arcos

Montoni

et al. 2021

Toxins

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Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 μg/mL (low) or 2.5 μg/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival.

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Section: Methodsmentioning

confidence: 99%

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Kisaki

Arcos

Montoni

et al. 2021

Toxins

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“…Liquid chromatography was performed using a house-prepared analytical and precolumn C18 column as previously described. 15 A linear gradient from 5 to 80% of acetonitrile in 0.1% FA during 15 min at a 1 μL/min flow was used. The spectrometer was set to a positive parameter.…”

Section: Methodsmentioning

confidence: 99%

“…The samples were diluted in 10 μL of 0.1% formic acid (FA) prior to injection. Liquid chromatography was performed using a house-prepared analytical and precolumn C18 column as previously described . A linear gradient from 5 to 80% of acetonitrile in 0.1% FA during 15 min at a 1 μL/min flow was used.…”

Section: Methodsmentioning

confidence: 99%

Protein Components of the Arthrodial Membrane Gland in a Neotropical Harvestman (Arachnida, Opiliones)

et al. 2021

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The content of arthrodial membrane glands in arthropods has seldom been studied. Here, we have analyzed the proteins of the arthrodial membrane gland of the trochanter–coxa articulation of the fourth pair of legs in the harvestman Mischonyx cuspidatus via reverse-phase high-performance liquid chromatography (RP-HPLC), polyacrylamide gel electrophoresis (PAGE), and nanoscale liquid chromatography coupled to mass spectrometry (nLC-MS/MS) analysis. Most of the fractions studied are hydrophobic, being proteins with molecular weights of ∼28, 62, and ∼198 kDa. These proteins seem to be homologous to proteins involved in product secretion, cytoskeleton, protein binding, cellular metabolism, and antimicrobial action among others. Lubricant function is also possible based on the literature. We were able to identify 147 proteins in the inner region, 91 proteins from the outer dorsal region, and 36 proteins from the outer ventral region. Some proteins are present only in one of these regions and some are shared by one or more regions. Our work provides, to the best of our knowledge, the first proteome characterization of the content of an arthrodial membrane gland in arachnids. Dataset Identifier: ftp://massive.ucsd.edu/MSV000087195/.

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“…A synthetic recombinant peptide against short-chain α-neurotoxin (ScNtx) was developed to neutralize the venoms of diverse genera such as Micrurus , Dendroaspis , Naja , and Walterinnesia [ 127 ]. Another proteomics study further pointed out the protein landscapes of the venom, which provides a platform for synaptic inhibitor development [ 128 ].…”

Section: Treatmentmentioning

confidence: 99%

Cerebral Complications of Snakebite Envenoming: Case Studies

Lin

Chen

Liu

et al. 2022

Toxins

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There are an estimated 5.4 million snakebite cases every year. People with snakebite envenoming suffer from severe complications, or even death. Although some review articles cover several topics of snakebite envenoming, a review of the cases regarding cerebral complications, especially rare syndromes, is lacking. Here, we overview 35 cases of snakebite by front-fanged snakes, including Bothrops, Daboia, Cerastes, Deinagkistrodon, Trimeresurus, and Crotalus in the Viperidae family; Bungarus and Naja in the Elapidae family, and Homoroselaps (rare cases) in the Lamprophiidae family. We also review three rare cases of snakebite by rear-fanged snakes, including Oxybelis and Leptodeira in the Colubridae family. In the cases of viper bites, most patients (17/24) were diagnosed with ischemic stroke and intracranial hemorrhage, leading to six deaths. We then discuss the potential underlying molecular mechanisms that cause these complications. In cases of elapid bites, neural, cardiac, and ophthalmic disorders are the main complications. Due to the small amount of venom injection and the inability to deep bite, all the rear-fanged snakebites did not develop any severe complications. To date, antivenom (AV) is the most effective therapy for snakebite envenoming. In the six cases of viper and elapid bites that did not receive AV, three cases (two by viper and one by elapid) resulted in death. This indicates that AV treatment is the key to survival after a venomous snakebite. Lastly, we also discuss several studies of therapeutic agents against snakebite-envenoming-induced complications, which could be potential adjuvants along with AV treatment. This article organizes the diagnosis of hemotoxic and neurotoxic envenoming, which may help ER doctors determine the treatment for unidentified snakebite.

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

Cited by 8 publications

References 68 publications

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Protein Components of the Arthrodial Membrane Gland in a Neotropical Harvestman (Arachnida, Opiliones)

Cerebral Complications of Snakebite Envenoming: Case Studies

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