title: The involvement of GSH in the activation of human Sod1 linked to FALS in chronologically aged yeast cells.
abstract: Mutations in Cu, Zn-superoxide dismutase (Sod1) have been associated with familial amyotrophic lateral sclerosis, an age-related disease. Because several studies suggest that oxidative stress plays a central role in neurodegeneration, we aimed to investigate the role of the antioxidant glutathione (GSH) in the activation of human A4V Sod1 during chronological aging. Transformation of wild-type and A4V hSod1 into a gsh null mutant and in its parental strain of Saccharomyces cerevisiae indicated that during aging, the number of viable cells was strongly influenced by A4V hSod1 mainly in cells lacking GSH. Activity of hSod1 increased in response to aging, although the increase observed in A4V hSod1 was almost 60% lower. Activation of hSod1 (A4V and WT) did not occur after aging, in cells lacking GSH, but could still be observed in the absence of Ccs1. Furthermore, no increase in activity could be seen in grx1 and grx2 null mutants, suggesting that glutathionylation is essential for hSod1 activation. The A4V mutation as well as the absence of GSH, reduced hSod1 activity, and increased oxidative damage after aging. In conclusion, our results point to a GSH requirement for hSod1 Ccs1-independent activation as well as for protection of hSod1 during the aging process.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: Brasil
authors.forename: Allan
authors.initials: A
authors.lastname: Belati
authors.forename: Sérgio C
authors.initials: SC
authors.lastname: Mannarino
authors.forename: Anita D
authors.initials: AD
authors.lastname: Panek
authors.forename: Elis C A
authors.initials: EC
authors.lastname: Eleutherio
authors.forename: Marcos D
authors.initials: MD
authors.lastname: Pereira
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C491960:CCS1 protein, S cerevisiae; D054477:Glutaredoxins; C530831:Grx1 protein, S cerevisiae; C527885:Grx2 protein, S cerevisiae; D018832:Molecular Chaperones; C000606290:SOD1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione
keywords: A4V hSod1; GSH; Saccharomyces cerevisiae; aging; familial amyotrophic lateral sclerosis; hSod1