title: Stigmurin and TsAP-2 from Tityus stigmurus scorpion venom: Assessment of structure and therapeutic potential in experimental sepsis.
abstract: Microbial resistance to conventional antibiotics is a public health problem worldwide, motivating the search for new therapeutic alternatives in varied natural sources. Cationic peptides without disulfide bridges from scorpions have been targeted in this context, mainly due to their multifunctional action and the limited ability of microorganisms to develop resistance against them. The present study was focused on Stigmurin and TsAP-2, cationic peptides found in the transcriptome of the venom gland from the scorpion Tityus stigmurus. The aims were: to assess the secondary structure of TsAP-2 and the structural stability of both peptides by circular dichroism; to evaluate their antiproliferative effect, and antimicrobial activities in vitro, ex vivo and in vivo; and to investigate their therapeutic potential in a murine model of polymicrobial sepsis. Stigmurin and TsAP-2 secondary structures responded similarly to environment polarity changes, and were stable to temperature and pH variation. Both peptides showed antiproliferative effect on tumor cells. TsAP-2 showed lower cytotoxicity to normal cells, and had a mitogenic activity on murine macrophages. Stigmurin demonstrated bactericidal and bacteriostatic activity, depending on the microorganism, whereas TsAP-2 had bactericidal action upon different bacterial strains analyzed. Both peptides were able to reduce leukocyte migration, TNF-α levels and microorganism load in the peritoneal cavity after induction of experimental sepsis, decreasing inflammation in the lung and cecum of septic animals. TsAP-2 also reduced the release of nitric oxide in the peritoneal cavity. Taken together, these data suggest that Stigmurin and TsAP-2 are structurally stable molecules and are efficient in the control of the infectious focus in polymicrobial sepsis, with potential use as a prototype for the rational design of novel therapeutic agents.
authors: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Alessandra
authors: A
authors: Daniele-Silva
authors: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Richele J A
authors: RJ
authors: Machado
authors: Instituto de Química, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Norberto K V
authors: NK
authors: Monteiro
authors: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Andréia B
authors: AB
authors: Estrela
authors: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Elizabeth C G
authors: EC
authors: Santos
authors: Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil.
authors: Eneas
authors: E
authors: Carvalho
authors: Departamento de Morfologia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Raimundo F
authors: RF
authors: Araújo Júnior
authors: Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Raniere F
authors: RF
authors: Melo-Silveira
authors: Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Hugo Alexandre O
authors: HA
authors: Rocha
authors: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Arnóbio A
authors: AA
authors: Silva-Júnior
authors: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address: mpedrosa@ufrnet.br.
authors: Matheus F
authors: MF
authors: Fernandes-Pedrosa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002942:Circular Dichroism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000378:metabolism; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity*; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013696:Temperature; D014118:Toxins, Biological / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D012604:Scorpion Venoms; D014118:Toxins, Biological; C000618389:stigmurin, Tityus stigmurus; D009569:Nitric Oxide
keywords: Antimicrobial peptides; Antiproliferative; Scorpion; Sepsis; Structural assessment