Experimental inhibition of a key cellular antioxidant affects vocal communication

1. There is substantial interest of evolutionary ecologists in the proximate mechanisms that modulate vocal communication. In recent times, there has been growing interest in the role of oxidative stress as a mediator of avian song expression. 2. Here, we tested whether the experimental inhibition of the synthesis of a key cellular antioxidant (glutathione) reduces song rate metrics of male European starlings (Sturnus vulgaris). We measured the effect of our treatment on total song rate and on its two components, undirected and nest-box-oriented song, outside the breeding season. 3. Treated males that did not own a nest-box (subordinate males likely to be of lower quality) suffered increased oxidative stress relative to untreated males, while treated males that owned a nest-box (dominant males likely to be of higher quality) did not. Treated non-owners also reduced their undirected song rate, whereas treated nest-box owners did not suffer any reduction in song rate. 4. Our results revealed that inhibition of a key cellular antioxidant results in decreased vocal communication in a social vertebrate, and that this effect is dependent on its social status (nest-box owner vs. non-owner). 5. This work provides support for the hypothesis that acoustic signals may honestly convey information about the individual oxidative status and capacity to regulate the oxidative balance. Our findings raise the possibility of hitherto unexplored impacts of oxidative stress on fitness traits in social species

Dissecting the role of glutathione biosynthesis in Plasmodium falciparum

Glutathione (γ-glutamylcysteinyl-glycine, GSH) has vital functions as thiol redox buffer and cofactor of antioxidant and detoxification enzymes. Plasmodium falciparum possesses a functional GSH biosynthesis pathway and contains mM concentrations of the tripeptide. It was impossible to delete in P. falciparum the genes encoding γ-glutamylcysteine synthetase (γGCS) or glutathione synthetase (GS), the two enzymes synthesizing GSH, although both gene loci were not refractory to recombination. Our data show that the parasites cannot compensate for the loss of GSH biosynthesis via GSH uptake. This suggests an important if not essential function of GSH biosynthesis pathway for the parasites. Treatment with the irreversible inhibitor of γGCS L-buthionine sulfoximine (BSO) reduced intracellular GSH levels in P. falciparum and was lethal for their intra-erythrocytic development, corroborating the suggestion that GSH biosynthesis is important for parasite survival. Episomal expression of γgcs in P. falciparum increased tolerance to BSO attributable to increased levels of γGCS. Concomitantly expression of glutathione reductase was reduced leading to an increased GSH efflux. Together these data indicate that GSH levels are tightly regulated by a functional GSH biosynthesis and the reduction of GSSG

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors