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The involvement of GSH in the activation of human Sod1 linked to FALS in chronologically aged yeast cells.
FEMS Yeast Res. 2013 Aug; 13(5):433-40.FY

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+Show Affiliations

Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23496883

Citation

Brasil, Aline A., et al. "The Involvement of GSH in the Activation of Human Sod1 Linked to FALS in Chronologically Aged Yeast Cells." FEMS Yeast Research, vol. 13, no. 5, 2013, pp. 433-40.
Brasil AA, Belati A, Mannarino SC, et al. The involvement of GSH in the activation of human Sod1 linked to FALS in chronologically aged yeast cells. FEMS Yeast Res. 2013;13(5):433-40.
Brasil, A. A., Belati, A., Mannarino, S. C., Panek, A. D., Eleutherio, E. C., & Pereira, M. D. (2013). The involvement of GSH in the activation of human Sod1 linked to FALS in chronologically aged yeast cells. FEMS Yeast Research, 13(5), 433-40. https://doi.org/10.1111/1567-1364.12045
Brasil AA, et al. The Involvement of GSH in the Activation of Human Sod1 Linked to FALS in Chronologically Aged Yeast Cells. FEMS Yeast Res. 2013;13(5):433-40. PubMed PMID: 23496883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The involvement of GSH in the activation of human Sod1 linked to FALS in chronologically aged yeast cells. AU - Brasil,Aline A, AU - Belati,Allan, AU - Mannarino,Sérgio C, AU - Panek,Anita D, AU - Eleutherio,Elis C A, AU - Pereira,Marcos D, Y1 - 2013/04/04/ PY - 2012/10/18/received PY - 2013/03/11/revised PY - 2013/03/11/accepted PY - 2013/3/19/entrez PY - 2013/3/19/pubmed PY - 2014/1/31/medline KW - A4V hSod1 KW - GSH KW - Saccharomyces cerevisiae KW - aging KW - familial amyotrophic lateral sclerosis KW - hSod1 SP - 433 EP - 40 JF - FEMS yeast research JO - FEMS Yeast Res VL - 13 IS - 5 N2 - 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. SN - 1567-1364 UR - https://www.unboundmedicine.com/medline/citation/23496883/The_involvement_of_GSH_in_the_activation_of_human_Sod1_linked_to_FALS_in_chronologically_aged_yeast_cells_ L2 - https://academic.oup.com/femsyr/article-lookup/doi/10.1111/1567-1364.12045 DB - PRIME DP - Unbound Medicine ER -