Disease relevance of AHP1

• 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 [1].

High impact information on AHP1

• We found a new stable form of alkyl hydroperoxide reductase 1 (Ahp1) with a lower isoelectric point [2].
• Identification in Saccharomyces cerevisiae of a new stable variant of alkyl hydroperoxide reductase 1 (Ahp1) induced by oxidative stress [2].
• In addition to two yeast TPx isoforms (TSA I and TSA II/AHPC1) previously described, three additional TPx homologues were identified by analysis of the open reading frame data base for Saccharomyces cerevisiae [3].
• Therefore, with respect to substrate specificity, Ahp1p differs from Tsa1p and is similar to prokaryotic alkyl hydroperoxide reductase AhpC [4].
• Under these high-DHA conditions expression of several stress-related proteins, e.g. a heat-shock protein (Hsp104p) and the oxidative stress indicator, alkyl hydroperoxide reductase (Ahp1p) was also found induced [5].

Chemical compound and disease context of AHP1

• 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 [1].

Biological context of AHP1

• Based on Mn2+ transport data, we concluded that Ahp1p is involved in cellular Mn2+ homeostasis in trafficking of Mn2+ from cytosol to mitochondria and from cytosol for export across the plasma membrane [6].

Anatomical context of AHP1

• We found that a GFP-Ahp1p fusion construct was in the cytosol when cells were grown in glucose, and in the mitochondria when cells were grown in oleate [6].

Associations of AHP1 with chemical compounds

• These data suggest that Ahp1p is a yeast orthologue of prokaryotic AhpC and justifies its name of yeast alkyl hydroperoxide reductase [4].
• A surfactant, sodium N-lauroyl sarcosinate (SLS), enhanced the solubilization of a few proteins including alkyl hydroperoxide reductase 1 (AHP1) in intact cells, accounting for the absence of this protein in the extract from allicin-treated cells [7].
• Our study suggests that allicin influences the mode of cell surface localization or the related function of AHP1 as a defense against phospholipid peroxidation by the external action of Cu(2+) [7].
• Allicin-treated cells and SLS-treated cells similarly showed an increased sensitivity to exogenously added tert-butyl hydroperoxide (t-BOOH), an organic peroxide that is detoxified by the action of AHP1 [7].
• In vitro treatment of Ahp1 by a large excess of tBuOOH leads to an inactive form, with the catalytic cysteine overoxidized into sulfonate, as demonstrated by (13)C NMR [8].

Other interactions of AHP1

• A second gene, AHP1, was cloned as a suppressor of the Mn2+ tolerance of a delta cmp1 delta cmp2 pmr1 mutant [6].
• Moreover, treatment of cells with thiol-specific oxidants affects the abundance of Ahp1p-Urm1p conjugates [9].
• We show results suggesting that during the adaptation period preceding the resumption of inhibited exponential growth under herbicide stress, the antioxidant enzyme Ahp1p and the heat shock proteins Hsp12p and Ssb2p (or Ssb1p) are present in higher amounts [10].
• Attachment of the ubiquitin-related protein Urm1p to the antioxidant protein Ahp1p [9].

References