RESUMO
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.
Assuntos
Animais , Bothrops/classificação , Venenos de Serpentes/efeitos adversos , Pré-EclâmpsiaRESUMO
Bradykinin potentiating peptides (BPPs) from Bothrops jararaca venom were first described in the middle of 1960s and were the first natural inhibitors of the angiotensin-converting enzyme (ACE). BPPs present a classical motif and can be recognized by their typical pyroglutamyl (Pyr)/proline rich sequences presenting, invariably, a proline residue at the C-terminus. In the present study, we describe the isolation and biological characterization of a novel BPP isolated from the skin secretion of the Brazilian tree-frog Phyllomedusa hypochondrialis. This new BPP, named Phypo Xa presents the sequence Pyr-Phe-Arg-Pro-Ser-Tyr-Gln-Ile-Pro-Pro and is able to potentiate bradykinin activities in vivo and in vitro, as well as efficiently and competitively inhibit ACE. This is the first canonical BPP (i.e. Pyr-Aaan-Gln-Ile-Pro-Pro) to be found not only in the frog skin but also in any other natural source other than the snake venoms.
Assuntos
Animais , Anfíbios/classificação , Serpentes/classificação , Venenos de Anfíbios/toxicidade , Venenos de Serpentes/toxicidadeRESUMO
The Center for Applied Toxinology (CAT), an institutional research organization based at the Butantan Institute, is one of the several Centers of Research, Innovation and Dissemination (CEPID) created in September 1998. CEPID, a pioneering program of the The State of São Paulo Research Foundation (FAPESP), was established to stimulate research, disseminate knowledge and foster contact between science and industry. CAT aims at conducting research on compounds derived from naturally occurring toxins, which might be of medical, ecological and economic interest. CAT takes a multidisciplinary approach in the investigation of natural toxins, including isolation and purification, pharmacological action, structural determination, structure-function studies, and molecular biology aspects. The following institutions will be involved in this endeavor: University of São Paulo (USP) [Marine Biology Center; Departments of Physiology and Anatomy, Institute for Biomedical Sciences; Department of Biochemistry, Institute of Chemistry]; São Paulo State University (UNESP) [Laboratory of Structural Biology and Zoochemistry, Institute of Biosciences, Rio Claro; Laboratory of Crystallography, Department of Physics, Institute of Biosciences, Humanities, and Exact Sciences, São José do Rio Preto]; and the Federal University of São Paulo (UNIFESP).(AU)
Assuntos
Bioquímica , Preparações Farmacêuticas , Cristalografia , Indústrias , Biologia Marinha , ToxicologiaRESUMO
Este artigo pretende mostrar que a pesquisa científica, que há um século marcou as vidas de Adolfo Lutz, Oswaldo Cruz, Vital Brasil, Carlos Chagas e Rocha Lima, continua sendo a condição essencial para resolver problemas de saúde no Brasil. Optar por caminhos mais curtos, além de nos condenar ao subdesenvolvimento, consagra a contradição entre sermos capazes de elucidar o genoma de uma bactéria patogênica e continuarmos importando produtos e tecnologias e exportando, a fundo perdido, nossas riquezas e inovações.