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
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 a...
Guardado en:
Autores principales: | , , , |
---|---|
Formato: | Artículo publishedVersion |
Lenguaje: | Inglés |
Publicado: |
2002
|
Materias: | |
Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00219258_v277_n14_p11896_PiwienPilipuk |
Aporte de: |
id |
paperaa:paper_00219258_v277_n14_p11896_PiwienPilipuk |
---|---|
record_format |
dspace |
spelling |
paperaa:paper_00219258_v277_n14_p11896_PiwienPilipuk2023-06-12T16:42:49Z 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 J. Biol. Chem. 2002;277(14):11896-11903 Piwien-Pilipuk, G. Ayala, A. Machado, A. Galigniana, M.D. Biological organs Carbonylation Cells Monomers Oligomers Proteins Oxidative stress Biochemistry buthionine sulfoximine elongation factor 2 mineralocorticoid receptor adenosine diphosphate ribosylation aging animal cell animal model article controlled study correlation analysis cytosol hormone binding inhibition kinetics male mouse nonhuman oxidative stress priority journal protein degradation protein depletion protein expression protein modification protein processing protein structure structure analysis translation initiation ADP-Ribosylation Factors Aging Animals Antimetabolites Buthionine Sulfoximine Cytosol Enzyme Inhibitors Glutathione HSP90 Heat-Shock Proteins Kidney Male Mice Mice, Inbred BALB C Oxidation-Reduction Oxidative Stress Oxygen Peptide Elongation Factor 2 Polyribosomes Precipitin Tests Protein Binding Protein Biosynthesis Protein Processing, Post-Translational Receptors, Mineralocorticoid Reticulocytes Time Factors Transcription, Genetic Animalia 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. 2002 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v277_n14_p11896_PiwienPilipuk |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
language |
Inglés |
orig_language_str_mv |
eng |
topic |
Biological organs Carbonylation Cells Monomers Oligomers Proteins Oxidative stress Biochemistry buthionine sulfoximine elongation factor 2 mineralocorticoid receptor adenosine diphosphate ribosylation aging animal cell animal model article controlled study correlation analysis cytosol hormone binding inhibition kinetics male mouse nonhuman oxidative stress priority journal protein degradation protein depletion protein expression protein modification protein processing protein structure structure analysis translation initiation ADP-Ribosylation Factors Aging Animals Antimetabolites Buthionine Sulfoximine Cytosol Enzyme Inhibitors Glutathione HSP90 Heat-Shock Proteins Kidney Male Mice Mice, Inbred BALB C Oxidation-Reduction Oxidative Stress Oxygen Peptide Elongation Factor 2 Polyribosomes Precipitin Tests Protein Binding Protein Biosynthesis Protein Processing, Post-Translational Receptors, Mineralocorticoid Reticulocytes Time Factors Transcription, Genetic Animalia |
spellingShingle |
Biological organs Carbonylation Cells Monomers Oligomers Proteins Oxidative stress Biochemistry buthionine sulfoximine elongation factor 2 mineralocorticoid receptor adenosine diphosphate ribosylation aging animal cell animal model article controlled study correlation analysis cytosol hormone binding inhibition kinetics male mouse nonhuman oxidative stress priority journal protein degradation protein depletion protein expression protein modification protein processing protein structure structure analysis translation initiation ADP-Ribosylation Factors Aging Animals Antimetabolites Buthionine Sulfoximine Cytosol Enzyme Inhibitors Glutathione HSP90 Heat-Shock Proteins Kidney Male Mice Mice, Inbred BALB C Oxidation-Reduction Oxidative Stress Oxygen Peptide Elongation Factor 2 Polyribosomes Precipitin Tests Protein Binding Protein Biosynthesis Protein Processing, Post-Translational Receptors, Mineralocorticoid Reticulocytes Time Factors Transcription, Genetic Animalia Piwien-Pilipuk, G. Ayala, A. Machado, A. Galigniana, M.D. 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 |
topic_facet |
Biological organs Carbonylation Cells Monomers Oligomers Proteins Oxidative stress Biochemistry buthionine sulfoximine elongation factor 2 mineralocorticoid receptor adenosine diphosphate ribosylation aging animal cell animal model article controlled study correlation analysis cytosol hormone binding inhibition kinetics male mouse nonhuman oxidative stress priority journal protein degradation protein depletion protein expression protein modification protein processing protein structure structure analysis translation initiation ADP-Ribosylation Factors Aging Animals Antimetabolites Buthionine Sulfoximine Cytosol Enzyme Inhibitors Glutathione HSP90 Heat-Shock Proteins Kidney Male Mice Mice, Inbred BALB C Oxidation-Reduction Oxidative Stress Oxygen Peptide Elongation Factor 2 Polyribosomes Precipitin Tests Protein Binding Protein Biosynthesis Protein Processing, Post-Translational Receptors, Mineralocorticoid Reticulocytes Time Factors Transcription, Genetic Animalia |
description |
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. |
format |
Artículo Artículo publishedVersion |
author |
Piwien-Pilipuk, G. Ayala, A. Machado, A. Galigniana, M.D. |
author_facet |
Piwien-Pilipuk, G. Ayala, A. Machado, A. Galigniana, M.D. |
author_sort |
Piwien-Pilipuk, G. |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publishDate |
2002 |
url |
http://hdl.handle.net/20.500.12110/paper_00219258_v277_n14_p11896_PiwienPilipuk |
work_keys_str_mv |
AT piwienpilipukg impairmentofmineralocorticoidreceptormrdependentbiologicalresponsebyoxidativestressandagingcorrelationwithposttranslationalmodificationofmranddecreasedadpribosylatablelevelofelongationfactor2inkidneycells AT ayalaa impairmentofmineralocorticoidreceptormrdependentbiologicalresponsebyoxidativestressandagingcorrelationwithposttranslationalmodificationofmranddecreasedadpribosylatablelevelofelongationfactor2inkidneycells AT machadoa impairmentofmineralocorticoidreceptormrdependentbiologicalresponsebyoxidativestressandagingcorrelationwithposttranslationalmodificationofmranddecreasedadpribosylatablelevelofelongationfactor2inkidneycells AT galignianamd impairmentofmineralocorticoidreceptormrdependentbiologicalresponsebyoxidativestressandagingcorrelationwithposttranslationalmodificationofmranddecreasedadpribosylatablelevelofelongationfactor2inkidneycells |
_version_ |
1769810316688883712 |