Impairment of mineralocorticoid receptor (MR)-dependent biological response by oxidative stress and aging: Correlation with post-translational modification of MR and decreased ADP-ribosylatable level of elongation factor 2 in kidney cells
| Autor: | Piwien-Pilipuk, G., Ayala, A., Machado, A., Galigniana, M.D. |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Male
Aging Reticulocytes Time Factors Transcription Genetic hormone binding Antimetabolites correlation analysis animal cell Kidney Biochemistry buthionine sulfoximine Mice Cytosol Peptide Elongation Factor 2 adenosine diphosphate ribosylation oxidative stress Enzyme Inhibitors Mice Inbred BALB C ADP-Ribosylation Factors Monomers article protein processing Glutathione structure analysis priority journal protein degradation Oxidation-Reduction Protein Binding Cells Carbonylation translation initiation protein modification inhibition kinetics Animals Animalia controlled study HSP90 Heat-Shock Proteins protein structure protein expression mouse mineralocorticoid receptor elongation factor 2 nonhuman protein depletion animal model Proteins Biological organs Precipitin Tests Oxygen Receptors Mineralocorticoid Oligomers Polyribosomes Protein Biosynthesis Protein Processing Post-Translational |
| Zdroj: | J. Biol. Chem. 2002;277(14):11896-11903 Biblioteca Digital (UBA-FCEN) Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN |
| Popis: | Acute and chronic treatments of mice with the glutathione-depleting agent, L-buthionine-(SR)-sulfoximine (BSO), impaired the mineralocorticoid receptor (MR)-dependent biological response by inhibiting aldosterone 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 carbonylation. In addition, a failure at the elongation/termination 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 affected as in L-buthionine-(SR)-sulfoximine-treated young mice. We therefore propose that a dramatic depletion of glutathione in kidney cells mimics the cumulative effect of aging which, at the end, may lead to a renal mineralocorticoid dysfunction. |
| Databáze: | OpenAIRE |
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