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Ras‐selective lethal small molecule 3 (RSL3), a drug candidate prototype for cancer chemotherapy, triggers ferroptosis by inactivating the glutathione peroxidase glutathione peroxidase 4 (GPx4). Here, we report the purification of the protein indispensable for GPx4 inactivation by RSL3. Mass spectrometric analysis identified 14‐3‐3 isoforms as candidates, and recombinant human 14‐3‐3ε confirms the identification. The function of 14‐3‐3ε is redox‐regulated. Moreover, overexpression or silencing of the gene coding for 14‐3‐3ε consistently controls the inactivation of GPx4 by RSL3. The interaction of GPx4 with a redox‐regulated adaptor protein operating in cell signaling further contributes to frame it within redox‐regulated pathways of cell survival and death and opens new therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations have been used to study molecular encounters and recognition. In recent works, simulations using high concentration of interacting molecules have been performed. In this paper, we consider the practical problems for setting up the simulation and to analyse the results of the simulation. The simulation of beta 2-microglobulin association and the simulation of the binding of hydrogen peroxide by glutathione peroxidase are provided as examples. [ABSTRACT FROM AUTHOR]

Following our recent findings on the presence of human cytomegalovirus (HCMV) in the normal human adrenal cortex and in adrenocortical tumors, especially in cortisol-secreting tumors, aim of the present study was to investigate the direct effects of HCMV infection on human adrenocortical cells. To this aim, both clinical isolates and laboratory strains of HCMV were used to assess the early effects of infection on human adrenocortical cell morphology, proliferation, gene expression, and steroidogenic function. Both clinical and laboratory HCMV strains could infect and replicate in primary human adrenocortical cell cultures and in adrenocortical carcinoma cell lines, leading to cytopathic changes. Most importantly, in the first hours post-infection (p.i.), adrenocortical cells showed a significant increase of cortisol and estrogen production, paralleled by up-regulation of steroidogenic acute regulatory protein and expression of steroidogenic enzymes involved in the last steps of adrenal steroidogenesis. This effect was probably due to HCMV immediate-early gene expression, since it was most evident in the early phases p.i. and UV-inactivated viral particles did not affect hormone production. Moreover, the effect on steroidogenesis was HCMV specific, since it was not observed after infection with herpes simplex virus. These data suggest that human adrenocortical cells are permissive to HCMV infection and acutely respond to infection with increased cortisol production. An acute glucocorticoid response is typically triggered by infections and is considered to be critical to host defense against pathogens, although, in the case of HCMV infection, it might also enhance viral replication and reactivation from latency. J. Cell. Physiol. 221: 629–641, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

• Here, for the first time, a comprehensive transcriptomics study is presented of leaf senescence in the legume model Medicago truncatula, providing a broad overview of differentially expressed transcripts involved in this process. • The cDNA-amplification fragment length polymorphism (AFLP) technique was used to identify > 500 genes, which were cloned and sorted into functional categories according to their gene ontology annotation. • Comparison between the datasets of Arabidopsis and M. truncatula leaf senescence reveals common physiological events but differences in the nitrogen metabolism and in transcriptional regulation. In addition, it was observed that a minority of the genes regulated during leaf senescence were equally involved in other processes leading to programmed cell death, such as nodule senescence and nitric oxide signalling. • This study provides a wide transcriptional profile for the comprehension of key events of leaf senescence in M. truncatula and highlights a possible regulative role for MADS box transcription factors in the terminal phases of the process. [ABSTRACT FROM AUTHOR]

Abstract: Phospholipid hydroperoxide glutathione peroxidase is a monomeric Se-peroxidase highly expressed in mammalian male germ cells. Its nuclear form, sperm nuclei glutathione peroxidase (snGPx), has been originally identified in maturating spermatozoa as a transcription product containing an alternative exon within the phospholipid hydroperoxide glutathione peroxidase gene. In this paper, we show that this form is inconstantly detectable in rat spermatozoa where a 20.0 and 25.9kDa major forms are detected instead. These have been conclusively characterized. The N-terminus sequence of the 20.0 kDa form confirmed that the protein is identical to cytosolic form, suggesting diffusion into the nucleus. The 25.9kDa protein represented a truncated form of the previously described nuclear snGPx, lacking the basic nuclear localization signal. This protein is present in two forms differing from each other by the presence of an N-terminal methionine. The presence of traces of the larger snGPx form suggests that exhaustive proteolytic processing of the precursor produces the 25.9kDa enzyme, although the alternate use of a downstream ATG, at least in rodents, could not be unequivocally ruled out. [Copyright &y& Elsevier]