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dc.creatorPiwien Pilipuk, Gracielaes
dc.creatorAyala Gómez, Antonioes
dc.creatorMachado de la Quintana, Albertoes
dc.creatorGaligniana, Mario
dc.identifier.citationPiwien Pilipuk, G., Ayala Gómez, A., Machado de la Quintana, A. y Galigniana, M.D. (2002). Impairment of mineralocorticoid receptor (MR)-dependent biological response by oxidative stress and aging. Journal of Biological Chemistry, 277 (14), 11896-11903.
dc.description.abstractAcute and chronic treatments of mice with the gluta- thione-depleting agent, L-buthionine-(SR)-sulfoximine (BSO), impaired the mineralocorticoid receptor (MR)- dependent biological response by inhibiting aldoster- one binding. This steroid-binding inhibition was fully reversed when reducing agents were added to kidney cytosol obtained from mice treated for 5 h, but it was only partially reversed in cytosol obtained from mice treated for 10 days. Although the oligomeric structure of the MR-hsp90 heterocomplex was always unaffected, a decreased amount of MR protein was evidenced after the long term treatment. Such a deleterious effect was correlated with a post-translational modification of MR, as demonstrated by an increased level of receptor car- bonylation. In addition, a failure at the elongation/ter- mination step was also observed during the receptor translation process in a reticulocyte lysate system. Thus, a high polyribosomes/monomers ratio and both increased proteolysis and decreased ADP-ribosylatable concentration of elongation factor 2 (EF-2) were shown. Importantly, similar observations were also performed in vivo after depletion of glutathione. Notwithstanding the EF-2 functional disruption, not all renal proteins were equally affected as the MR. Interestingly, both EF-2 and MR expressed in old mice were similarly af- fected as in L-buthionine-(SR)-sulfoximine-treated young mice. We therefore propose that a dramatic de- pletion of glutathione in kidney cells mimics the cumu- lative effect of aging which, at the end, may lead to a renal mineralocorticoid
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes
dc.relation.ispartofJournal of Biological Chemistry, 277 (14), 11896-11903.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.titleImpairment of mineralocorticoid receptor (MR)-dependent biological response by oxidative stress and aginges
dc.title.alternativeCorrelation with post-translational modification of MR and decreased ADP-ribosylatable level of elongation factor 2 in kidney cellses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica y Biología Moleculares
dc.journaltitleJournal of Biological Chemistryes

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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