title: Bothrops jararaca peptide with anti-hypertensive action normalizes endothelium dysfunction involved in physiopathology of preeclampsia.
abstract: Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, is a major cause of fetal and maternal morbidity and mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide isolated from Bothrops jararaca venom, has been attributed with potent anti-hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti-hypertensive actions involved NO production in spontaneous hypertensive rats. Using in vitro studies we now show that Bj-PRO-10c was able to increase NO production in human umbilical vein endothelial cells from hypertensive pregnant women (HUVEC-PE) to levels observed in HUVEC of normotensive women. Moreover, in the presence of the peptide, eNOS expression as well as argininosuccinate synthase activity, the key rate-limiting enzyme of the citrulline-NO cycle, were enhanced. In addition, excessive superoxide production due to NO deficiency, one of the major deleterious effects of the disease, was inhibited by Bj-PRO-10c. Bj-PRO-10c induced intracellular calcium fluxes in both, HUVEC-PE and HUVEC, which, however, led to activation of eNOS expression only in HUVEC-PE. Since Bj-PRO-10c promoted biological effects in HUVEC from patients suffering from the disorder and not in normotensive pregnant women, we hypothesize that Bj-PRO-10c induces its anti-hypertensive effect in mothers with preeclampsia. Such properties may initiate the development of novel therapeutics for treating preeclampsia.
authors.affiliation: Center for Applied Toxinology-Centros de Pesquisa, Inovacio e Difusao, Instituto Butantan, Sao Paulo, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Benedetti
authors.forename: Katia L P
authors.initials: KL
authors.lastname: Morais
authors.forename: Juliano R
authors.initials: JR
authors.lastname: Guerreiro
authors.forename: Eduardo Fontana
authors.initials: EF
authors.lastname: de Oliveira
authors.forename: Mara Sandra
authors.initials: MS
authors.lastname: Hoshida
authors.forename: Leandro
authors.initials: L
authors.lastname: Oliveira
authors.forename: Nelson
authors.initials: N
authors.lastname: Sass
authors.forename: Ivo
authors.initials: I
authors.lastname: Lebrun
authors.forename: Henning
authors.initials: H
authors.lastname: Ulrich
authors.forename: Claudiana
authors.initials: C
authors.lastname: Lameu
authors.forename: Antonio Carlos Martins
authors.initials: AC
authors.lastname: de Camargo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000378:metabolism; D015153:Blotting, Western; D017837:Bothrops / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000473:pathology / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D009842:Oligopeptides; C569838:PRO-10c protein, Bothrops jararaca; D014757:Viper Venoms; D013481:Superoxides; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D001124:Argininosuccinate Synthase; D002118:Calcium