This property renders this peptide an attractive molecule for use in the development of new compounds for the

treatment of infectious diseases.”
“Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report the functional relevance of AZD5582 mouse one of such enzymes, the mitochondrial 2-Cys peroxiredoxin (mTXNPx), was investigated along the Leishmania infantum life cycle. mTXNPx null mutants (mtxnpx(-)) produced by a gene replacement strategy, while indistinguishable from wild type promastigotes, were found unable to thrive in a murine model of infection. Unexpectedly, however, Sotrastaurin nmr the avirulent phenotype of mtxnpx(-) was not due to lack of the peroxidase activity of mTXNPx as these behaved like controls when exposed to oxidants added exogenously or generated by macrophages during phagocytosis ex vivo. In line with this, mtxnpx(-) were also avirulent when inoculated into murine hosts unable to mount an effective oxidative phagocyte response

(B6.p47(phox-/-) and B6.RAG2(-/-) IFN-gamma(-/-) mice). Definitive conclusion that the peroxidase activity of mTXNPx is not required for parasite survival in mice was obtained by showing that a peroxidase-inactive version of this protein was competent in rescuing the non-infective phenotype of mtxnpx(-). A novel function is thus proposed for mTXNPx, that of a molecular chaperone, which may explain the impaired infectivity of the null mutants. This premise is based on

the observation that the enzyme is able to suppress the thermal aggregation of citrate synthase in vitro. Also, mtxnpx- were more sensitive than controls to a temperature shift from 25 degrees C to 37 degrees C, a phenotype reminiscent of organisms lacking specific chaperone genes. Collectively, the findings reported here change the paradigm which regards all trypanosomatid 2-Cys peroxiredoxins as peroxide-eliminating devices. Moreover, they demonstrate, for the first time, that these 2-Cys peroxiredoxins can be determinant for pathogenicity independently of their peroxidase activity.”
“While several studies have been conducted PRIMA-1MET price on the antioxidant properties of the beta-amino acid taurine, these studies all used concentrations lower than what is found physiologically. This study investigates the scavenging and antioxidant properties of physiological taurine concentrations against different reactive species. No reactivity between taurine and hydrogen peroxide was found; however, taurine exhibited significant scavenging potential against peroxyl radical, nitric oxide, and superoxide donors. This study also evaluated if taurine was able to minimize the in vitro CuZn-superoxide dismutase damage (SOD) induced by peroxynitrite.