Reactive oxygen species-dependent-NLRP3 inflammasome activation in human neutrophils induced by l-amino acid oxidase derived from Calloselasma rhodostoma venom

Paloschi, Mauro Valentino; Boeno, Charles Nunes; Lopes, Jéssica Amaral; Rego, Cristina Matiele Alves; Silva, Milena Daniela Souza; Santana, Hallison Mota; Serrath, Suzanne Nery; Ikenohuchi, Yoda Janaina; Farias, Braz Junior Campos; Felipin, Kátia Paula; Néry, Neriane Monteiro; Reis, Valdison Pereira dos; Lemos, Caleb Torres de Lima; Evangelista, Jaína Rodrigues; Setúbal, Sulamita da Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan

doi:10.1016/j.lfs.2022.120962

Cited by 13 publications

(17 citation statements)

References 86 publications

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“…The abundance of LAAO in C. rhodostoma venom proteome is approximately 7% [ 18 ]. The pathological role of this toxin in C. rhodostoma envenoming is unclear but could be related to local inflammatory responses as it stimulates neutrophil activation and the production of inflammatory mediators [ 105 ].…”

Section: Resultsmentioning

confidence: 99%

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan

et al. 2023

Toxins

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In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study de novo assembled and analyzed the venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM, Fragments Per Kilobase Million), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI > PII > PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensin-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%), and others (1.78%). The expressions of SVMP, CTL, and SVSP correlate with hemorrhagic, anti-platelet, and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) acts by inhibiting platelet aggregation. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitors), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (an ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

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Section: Resultsmentioning

confidence: 99%

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan

et al. 2023

Toxins

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“…The ability of LAAO to activate cells of the immune system, particularly human neutrophils, was reported by PONTES et al [17,18] and PALOSCHI et al [19][20][21] using an LAAO isolated from Calloselasma rhodostoma snake venom, named Cr-LAAO. This LAAO stimulates neutrophils chemotaxis, phagocytosis, production, and release of reactive oxygen species (ROS) through Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase complex activation, as well as the release of pro-inflammatory cytokines, myeloperoxidase, and lipid mediators.…”

Section: Introductionmentioning

confidence: 83%

“…The literature demonstrates the biological and pharmacological effects induced by LAAO, including apoptosis induction [8], cytotoxicity [9], induction or inhibition of platelet aggregation [10], hemorrhage [11], hemolysis [12], bactericidal effects [13,14], leishmanicidal effects [15], edema [16], and activation of human neutrophils [17][18][19][20][21]. Many of the biological effects of LAAOs are attributed to the secondary effects of H 2 O 2 produced during the enzymatic reaction [10,16,22,23].…”

Section: Introductionmentioning

confidence: 99%

“…This LAAO stimulates neutrophils chemotaxis, phagocytosis, production, and release of reactive oxygen species (ROS) through Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase complex activation, as well as the release of pro-inflammatory cytokines, myeloperoxidase, and lipid mediators. It also activates NLRP3 inflammasome [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action

Serrath,

Pontes,

Paloschi

et al. 2023

Toxins

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L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 μg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO’s ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.

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“…The abundance of LAAO in C. rhodostoma venom proteome is approximately 7% [13]. The pathological role of this toxin in C. rhodostoma envenoming is unclear but could be related to local inflammatory responses as it stimulates neutrophil activation and production of inflammatory mediators [100].…”

Section: L-amino Acid Oxidase (Laao)mentioning

confidence: 99%

<em>De Novo </em>Venom Gland Transcriptome Assembly and Characterization for <em>Calloselasma rhodostoma</em> (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan¹,

Tan²,

Ng³

et al. 2023

Preprint

View full text Add to dashboard Cite

In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study assembled and analyzed the de novo venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI&gt;PII&gt;PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensinogen-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%) and others (1.78%). The expressions of SVMP, CTL and SVSP correlate with hemorrhagic, anti-platelet and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) is platelet-inhibitory. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitor), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

show abstract

Reactive oxygen species-dependent-NLRP3 inflammasome activation in human neutrophils induced by l-amino acid oxidase derived from Calloselasma rhodostoma venom

Cited by 13 publications

References 86 publications

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action

<em>De Novo </em>Venom Gland Transcriptome Assembly and Characterization for <em>Calloselasma rhodostoma</em> (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

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