RESUMO
The N-methyl-(2S,4R)-trans-4-hydroxy-l-proline-enriched fraction (NMP) from Sideroxylon obtusifolium was evaluated as a neuroprotective agent in the intracerebroventricular (icv) pilocarpine (Pilo) model. To this aim, male mice were subdivided into sham (SO, vehicle), Pilo (300 µg/1 µL icv, followed by the vehicle per os, po) and NMP-treated groups (Pilo 300 µg/1 µL icv, followed by 100 or 200 mg/kg po). The treatments started one day after the Pilo injection and continued for 15 days. The effects of NMP were assessed by characterizing the preservation of cognitive function in both the Y-maze and object recognition tests. The hippocampal cell viability was evaluated by Nissl staining. Additional markers of damage were studied-the glial fibrillary acidic protein (GFAP) and the ionized calcium-binding adaptor molecule 1 (Iba-1) expression using, respectively, immunofluorescence and western blot analyses. We also performed molecular docking experiments revealing that NMP binds to the γ-aminobutyric acid (GABA) transporter 1 (GAT1). GAT1 expression in the hippocampus was also characterized. Pilo induced cognitive deficits, cell damage, increased GFAP, Iba-1, and GAT1 expression in the hippocampus. These alterations were prevented, especially by the higher NMP dose. These data highlight NMP as a promising candidate for the protection of the hippocampus, as shown by the icv Pilo model.
Assuntos
Hipocampo/efeitos dos fármacos , Hidroxiprolina/farmacologia , Fármacos Neuroprotetores/farmacologia , Sapotaceae/química , Estado Epiléptico/patologia , Animais , Comportamento Animal/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de GABA/química , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Hidroxiprolina/química , Infusões Intraventriculares , Masculino , Camundongos , Proteínas dos Microfilamentos/metabolismo , Simulação de Acoplamento Molecular , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/química , Pilocarpina/administração & dosagem , Pilocarpina/toxicidade , Plantas Medicinais/química , Estado Epiléptico/induzido quimicamenteRESUMO
Bradykinin related peptides (BRPs) present in the water-soluble secretion and freshly dissected skin fragments of Phyllomedusa hypochondrialis were investigated by mass spectrometry techniques. Eighteen BRPs, along with their post-translational modifications, were characterized in the secretion by de novo MS/MS sequencing and direct MALDI imaging experiments of the frog skin. These molecules revealed strong sequence similarities to the main plasma kinin of some mammals and reptiles. Such a diversity of molecules, within the same peptide family, belonging to a single amphibian species may be related to functional specializations of these peptides and a variety of corresponding receptors that might be present in a number of different predators. Also, a novel analog, [Val]1,[Thr]6-bradykinyl-Gln,Ser had its biological activity positively detected in cell culture expressing the human bradykinin B2 receptor and in guinea pig ileum preparations.
Assuntos
Bradicinina/análogos & derivados , Bradicinina/química , Ranidae/metabolismo , Sequência de Aminoácidos , Animais , Células CHO , Cricetinae , Cricetulus , Feminino , Cobaias , Humanos , Hidroxiprolina/química , Espectrometria de Massas , Dados de Sequência Molecular , Músculo Liso/citologia , Músculo Liso/metabolismo , Ranidae/classificação , Receptor B2 da Bradicinina/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , TransfecçãoRESUMO
In 55 placentae, collected at term from clinically normal pregnancies, hydroxyproline was assayed. Thirty were from mothers who smoke and 25 from nonsmokers. In placentae of smokers, hydroxyproline concentration was 42.77 +/- 8.77 micrograms/mg of tissue and in these of nonsmokers 22.52 +/- 7.46 micrograms/mg. Such high a difference discloses a large increment in placental collagen production in smokers, which may account for some of the noxious effects of tobacco on pregnancy.
PIP: Hydroxyproline was assayed in 55 placentae, collected at term from clinically normal pregnancies. 30 came from mothers who smoke and 25 from nonsmokers. In the placentae of smokers, hydroxyproline concentration was 42.77 +or- 8.77 mcg/mg of tissue and in those of nonsmokers, 22.52 +or- 7.46 mcg/mg. Such a high difference discloses a large increment in placental collagen production among smokers, which may account for some of the noxious effects of tobacco on pregnancy.