2022-08-122022-08-122002Piwien 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), 11896-11903.0021-92581083-351Xhttps://hdl.handle.net/11441/136177Acute 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 dysfunction.application/pdf8 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1074/jbc.M109530200