title: Neuropeptide Y family-degrading metallopeptidases in the Tityus serrulatus venom partially blocked by commercial antivenoms.
abstract: Accidents caused by scorpions represent a relevant public health issue in Brazil, being more recurring than incidents with snakes and spiders. The main species responsible for this situation is the yellow scorpion, Tityus serrulatus, due especially to the great frequency with which accidents occur and the potential of its venom to induce severe clinical manifestations, even death, mainly among children. Although neurotoxins are well characterized, little information is known about other components of scorpion venoms, such as peptidases, and their effect on envenomation. Previous results from our group showed that the metallopeptidases present in this venom are capable of hydrolyzing the neuropeptide dynorphin 1-13 in vitro, releasing Leu-enkephalin, which may interact with ion channels and promote indirect neurotoxicity. Thus, this study aims to get more information about the effect of toxic peptidase activity present in the venom on biologically active peptides, and to evaluate the in vitro neutralizing potential of commercial antivenoms produced by the Butantan Institute. A set of human bioactive peptides were studied as substrates for the peptidases, and the members of the neuropeptide Y family were found to be the most susceptible ones. All new substrate hydrolyses were totally inhibited by ethylenediaminetetracetic and not blocked by phenylmethanesulfonylfluoride, indicating that metallopeptidases were responsible for the peptidase activity. Also, peptidase activities were only partially inhibited by therapeutic Brazilian scorpion antivenom (SAV) and arachnid antivenom (AAV). The dose-response inhibition by both antivenoms indicates that AAV neutralizes better than SAV at the used doses. These characterizations, unpublished until now, can contribute to the improvement of our knowledge about the venom and envenomation processes by T. serrulatus.
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cajado Carvalho
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil.
authors.forename: Alexandre K
authors.initials: AK
authors.lastname: Kuniyoshi
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil.
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Kodama
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil.
authors.forename: Ana K
authors.initials: AK
authors.lastname: Oliveira
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil.
authors.forename: Solange M T
authors.initials: SM
authors.lastname: Serrano
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil.
authors.forename: Denise V
authors.initials: DV
authors.lastname: Tambourgi
authors.affiliation: *Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil and Special Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling-CeTICS, Instituto Butantan, Brazil fernanda.portaro@butantan.gov.br.
authors.forename: Fernanda V
authors.initials: FV
authors.lastname: Portaro
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D031541:Fluorescence Resonance Energy Transfer; D006868:Hydrolysis; D013058:Mass Spectrometry; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D009478:Neuropeptide Y / Q000737:chemistry / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D012604:Scorpion Venoms / Q000201:enzymology*; D012605:Scorpions
chemical_list: D000997:Antivenins; D009478:Neuropeptide Y; D009479:Neuropeptides; D012604:Scorpion Venoms; D045726:Metalloproteases
keywords: Tityus serrulatus; antivenoms; bioactive peptides; metallopeptidases; venoms