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1.
Int J Mol Sci ; 20(24)2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31888202

RESUMO

Serine proteases constitute the major protein content of mast cell (MC) secretory granules. These proteases can generally be subdivided into chymases and tryptases based on their primary cleavage specificity. Here, we presented the extended cleavage specificities of a rabbit ß-chymase and a guinea pig α-chymase. Analyses by phage display screening and a panel of recombinant substrates showed a marked similarity in catalytic activity between the enzymes, both being strict Leu-ases (cleaving on the carboxyl side of Leu). Amino acid sequence alignment of a panel of mammalian chymotryptic MC proteases and 3D structural modeling identified an unusual residue in the rabbit enzyme at position 216 (Thr instead of more common Gly), which is most likely critical for the Leu-ase specificity. Almost all mammals studied, except rabbit and guinea pig, express classical chymotryptic enzymes with similarly extended specificities, indicating an important role of chymase in MC biology. The rabbit and guinea pig are the only two mammalian species currently known to lack a classical MC chymase. Key questions are now how this major difference affects their MC function, and if genes of other loci can rescue the loss of a chymotryptic activity in MCs of these two species.


Assuntos
Quimases/metabolismo , Leucina/metabolismo , Mastócitos/enzimologia , Sequência de Aminoácidos , Animais , Domínio Catalítico , Técnicas de Visualização da Superfície Celular , Quimases/química , Quimases/isolamento & purificação , Sequência Consenso , Ativação Enzimática , Cobaias , Células HEK293 , Humanos , Modelos Moleculares , Filogenia , Coelhos , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
2.
World J Microbiol Biotechnol ; 34(5): 64, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29671126

RESUMO

Staphylococcus aureus (S. aureus) is a common pathogenic bacterium that causes various diseases in both humans and animals. With the increased prevalence of methicillin-resistant S. aureus, the therapeutic effects of commonly used antibiotics are limited against S. aureus infection. Novel treatment strategies and new antibiotics are needed urgently to address this concern. Many studies have shown that virulence factors secreted from S. aureus play vital roles in their pathogenic processes. Alpha-hemolysin (Hla), an important exotoxin in S. aureus, is one such virulence factor that increases sensitivity of multiple host cells to S. aureus resulting in various diseases. Eriodictyol is a flavonoid compound that exists in many fruits and vegetables. In this study, eriodictyol was demonstrated to inhibit the expression of Hla by hemolysis assays, western blotting, and RT-qPCR at the sub-minimal inhibitory concentration. In live/dead and cytotoxicity assays, the results showed that eriodictyol protected A549 cells against Hla-induced injury in a dose-dependent manner. The minimal inhibitory concentration of eriodictyol against S. aureus was 512 µg/mL. Eriodictyol can downregulate S. aureus Hla at both the expressional and transcriptional levels without affecting S. aureus growth. In addition, cell assays had proved that eriodictyol could protect A549 cells against Hla damage. Eriodictyol could therefore have the potential to treat S. aureus infection targeting Hla.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/toxicidade , Flavanonas/farmacologia , Proteínas Hemolisinas/efeitos dos fármacos , Proteínas Hemolisinas/toxicidade , Lesão Pulmonar/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Células A549/efeitos dos fármacos , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Hemólise , Humanos , Lesão Pulmonar/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/patologia , Pneumonia Estafilocócica/prevenção & controle , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade , Fatores de Virulência/metabolismo
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