title: Insights into the Hypertensive Effects of Tityus serrulatus Scorpion Venom: Purification of an Angiotensin-Converting Enzyme-Like Peptidase.
abstract: The number of cases of envenomation by scorpions has grown significantly in Brazil since 2007, with the most severe cases being caused by theTityus serrulatusscorpion. Although envenomed patients mostly suffer neurotoxic manifestations, other symptoms, such as hypertension, cannot be exclusively attributed to neurotoxins. Omics analyses have detected plentiful amounts of metalloproteases inT. serrulatusvenom. However, the roles played by these enzymes in envenomation are still unclear. Endeavoring to investigate the functions of scorpion venom proteases, we describe here for the first time an Angiotensin I-Converting Enzyme-like peptidase (ACE-like) purified fromT. serrulatusvenom. The crude venom cleaved natural and fluorescent substrates and these activities were inhibited by captopril. Regarding the serum neutralization, the scorpion antivenom was more effective at blocking the ACE-like activity than arachnid antivenom, although neither completely inhibited the venom cleavage action, even at higher doses. ACE-like was purified from the venom after three chromatographic steps and its identity was confirmed by mass spectrometric and transcriptomic analyses. Bioinformatics analysis showed homology between the ACE-like transcript sequences fromTityusspp. and human testis ACE. These findings advance our understanding ofT. serrulatusvenom components and may improve treatment of envenomation victims, as ACE-like may contribute to envenomation symptoms, especially the resulting hypertension.
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo CEP 05503-900, SP, Brazil. daniela.carvalho@butantan.gov.br.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cajado-Carvalho
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo CEP 05503-900, SP, Brazil. alexandre.kuniyoshi@butantan.gov.br.
authors.forename: Alexandre Kazuo
authors.initials: AK
authors.lastname: Kuniyoshi
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo CEP 05503-900, SP, Brazil. bruno.duzzi@butantan.gov.br.
authors.forename: Bruno
authors.initials: B
authors.lastname: Duzzi
authors.affiliation: Special Laboratory for Applied Toxinology, Butantan Institute/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), São Paulo CEP 05503-900, SP, Brazil. leo.iwai@butantan.gov.br.
authors.forename: Leo Kei
authors.initials: LK
authors.lastname: Iwai
authors.affiliation: Special Laboratory for Applied Toxinology, Butantan Institute/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), São Paulo CEP 05503-900, SP, Brazil. ursula.oliveira@butantan.gov.br.
authors.forename: Úrsula Castro de
authors.initials: ÚC
authors.lastname: Oliveira
authors.affiliation: Special Laboratory for Applied Toxinology, Butantan Institute/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), São Paulo CEP 05503-900, SP, Brazil. inacio.azevedo@butantan.gov.br.
authors.forename: Inácio de Loiola Meirelles
authors.initials: IL
authors.lastname: Junqueira de Azevedo
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo CEP 05503-900, SP, Brazil. pararoberval@gmail.com.
authors.forename: Roberto Tadashi
authors.initials: RT
authors.lastname: Kodama
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo CEP 05503-900, SP, Brazil. fernanda.portaro@butantan.gov.br.
authors.forename: Fernanda Vieira
authors.initials: FV
authors.lastname: Portaro
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology*; D012605:Scorpions
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000997:Antivenins; D002712:Chlorides; D012604:Scorpion Venoms; D002216:Captopril; D010447:Peptide Hydrolases; D007703:Peptidyl-Dipeptidase A
keywords: ACE-like; Tityus serrulatus venom; antivenom; hypertension; proteases