172 resultados para chorismate synthase inhibitor


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Glycogen functions as a carbohydrate reserve in a variety of organisms and its metabolism is highly regulated. The activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of the synthesis and degradation processes, respectively, are regulated by allosteric modulation and reversible phosphorylation. To identify the protein kinases affecting glycogen metabolism in Neurospora crassa, we performed a screen of 84 serine/threonine kinase knockout strains. We identified multiple kinases that have already been described as controlling glycogen metabolism in different organisms, such as NcSNF1, NcPHO85, NcGSK3, NcPKA, PSK2 homologue and NcATG1. In addition, many hypothetical kinases have been implicated in the control of glycogen metabolism. Two kinases, NcIME-2 and NcNIMA, already functionally characterized but with no functions related to glycogen metabolism regulation, were also identified. Among the kinases identified, it is important to mention the role of NcSNF1. We showed in the present study that this kinase was implicated in glycogen synthase phosphorylation, as demonstrated by the higher levels of glycogen accumulated during growth, along with a higher glycogen synthase (GSN) ±glucose 6-phosphate activity ratio and a lesser set of phosphorylated GSN isoforms in strain Ncsnf1KO, when compared with the wild-type strain. The results led us to conclude that, in N. crassa, this kinase promotes phosphorylation of glycogen synthase either directly or indirectly, which is the opposite of what is described for Saccharomyces cerevisiae. The kinases also play a role in gene expression regulation, in that gdn, the gene encoding the debranching enzyme, was down-regulated by the proteins identified in the screen. Some kinases affected growth and development, suggesting a connection linking glycogen metabolism with cell growth and development.

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Nitric oxide (NO) is a free radical with participation in almost all physiologic host processes; however, in high concentrations it may damage the tissues. Its immunoregulatory action is present in the inflammation and in auto-immune mechanisms, being intensively studied in the medical area. Recently, some studies have also reported that NO could play a role as etiopathogenic factor of the periodontal disease, which shows inflammatory and multifactorial course. Due to beneficial or damage effects of NO, according to its concentrations, some studies have been focused in the evaluation of inhibitor of NO-Synthase (NOS) as therapeutic agents in inflammatory processes. In this context, the aim of this study was to report the role of NO and NOS inhibition in the periodontal disease modulation process. In conclusion, it could be suggested that NO seems to play an essential role in evolution of inflammatory periodontal disease, and that the NOS inhibition may be considered as a promising therapeutic in modulation of inflammatory process.

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Pós-graduação em Ciência Animal - FMVA

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