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Alkyl hydroperoxide reductase 1 (Ahp1p) is a thioredoxin peroxidase of the peroxiredoxin family expressed by Saccharomyces cerevisiae. Recently, disruption of the AHP1 gene has shown that the gene is not essential for yeast growth on glucose medium but revealed a high sensitivity of null mutants to organic peroxides, suggesting that Ahp1p is an important enzyme implicated in oxidative stress protection in S. cerevisiae. To gain insight into antioxidant enzymatic mechanisms involved in cell protection against metal toxicity and glutathione depletion, we investigated the resistance of S. cerevisiae, in which the AHP1 gene was disrupted, against several metals and diethyl maleate, a glutathione depleting agent. We report that Ahp1p protects yeast against toxicity induced by copper, cobalt, chromium, arsenite, arsenate, mercury, zinc and diethyl maleate, suggesting that Ahp1p plays an important role in S. cerevisiae in the protection against metals possibly by reducing peroxides generated in cells by these compounds.

Peroxiredoxin 5 (PRDX5) is a mammalian thioredoxin peroxidase ubiquitously expressed in tissues. Its role as antioxidant enzyme has been previously supported in different pathological situations. In this study, we determined the complete human PRDX5 genomic organization and isolated the 5'-flanking region of the gene. Human PRDX5 gene is composed of six exons and five introns similarly to other chordate PRDX5 genes. Several single nucleotide polymorphisms were identified. Six out of them have amino acid substitutions in protein-coding region. Analysis of the 5'-flanking region of human PRDX5 revealed the presence of a TATA-less promoter containing a canonical CpG island and several putative response elements for transcription factors. To analyze the regulatory mechanisms controlling human PRDX5 expression, we characterized the 5'-flanking region by cloning various segments of this region in front of a luciferase reporter sequence. Transfection in HepG2 cells indicate that the 5'-flanking region contains regulatory elements for constitutive expression of human PRDX5. Multiple transcription start sites were also identified by 5'-RACE-PCR in human liver. Moreover, although no corresponding proteins were reported, we present new alternative splicing variants encoded specifically by human PRDX5 gene. The characterization of human PRDX5 gene revealed the complexity of its regulation and a high variability of sequences that might be associated with pathological situations.

Human peroxiredoxin 5 is a recently discovered mitochondrial, peroxisomal and cytosolic thioredoxin peroxidase able to reduce hydrogen peroxide and alkyl hydroperoxides. To gain insight into peroxiredoxin 5 antioxidant role in cell protection, we investigated the resistance of yeast cells expressing human peroxiredoxin 5 in mitochondria or in the cytosol against oxidative stress induced by paraquat. The herbicide paraquat is a redox active drug known to generate superoxide anions in mitochondria and the cytosol of yeast and mammalian cells leading to the formation of several reactive oxygen species. Here, we report that mitochondrial and cytosolic human peroxiredoxin 5 protect yeast cells from cytotoxicity and lipid peroxidation induced by paraquat.