Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes.

The rat and yeast thiol-specifc antioxidant enzyme proteins show significant sequence homology to the 21-kDa component of Salnonela typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity

H. Z. Chae; K. Robison; L. B. Poole; G. Church; G. Storz; S. G. Rhee


Scholarcy highlights

  • A cDNA corresponding to a thiol-specifc antioxidant enzyme was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA
  • A rat brain Uni-ZAP XR cDNA library was screened with antibodies to bovine brain TSA
  • We report the isolation of cDNA corresponding to rat TSA and the corrected sequence of S. typhimurium AhpC, a component of alkyl hydroperoxide reductase
  • Attempts to identify any peroxidase activity inherent in the TSA protein have been hampered by the lack of a known reductase protein as a counterpart for the NAD(P)H-dependent AhpF of alkyl hydroperoxide reductase
  • We report that a large family of proteins is homologous to AhpC and TSA and that the family of proteins defined by AhpF and thioredoxin reductase has expanded to include six additional members
  • We have proposed that reactive sulfur species are substrates of TSA for several reasons. The antioxidant activity of TSA is observed only when a thiol compound is added to the metal-catalyzed oxidation system as electron donor; when thiol is replaced with another electron donor, no antioxidant activity is observed . TSA does not exhibit detectable catalase, superoxide dismutase, or glutathione peroxidase activity . The deduced amino acid sequence of yeast TSA shows no homology to any of the reactive oxygen species-specific antioxidant enzymes, such as superoxide dismutases, catalases, and peroxidases. Recently, the capacity of TSA to remove reactive sulfur species was directly demonstrated by electron paramagnetic resonance spectroscopy
  • In support of this hypothesis, some of the homologs were identified on the basis of their redox activities and at least eight of the AhpC/thiol-specifc antioxidant enzyme proteins are encoded near other genes encoding proteins that have oxidation-reduction activities

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