Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase

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Although transcriptional effects of thyroid hormones have substantial influence on oxidative metabolism, how thyroid sets basal metabolic rate remains obscure. Compartmental localization of nitric-oxide synthases is important for nitric oxide signaling. We therefore examined liver neuronal nitric-ox...

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Autores principales:	Franco, M.C., Antico Arciuch, V.G., Peralta, J.G., Galli, S., Levisman, D., López, L.M., Romorini, L., Poderoso, J.J., Carreras, M.C.
Formato:	JOUR
Materias:	Complexation Hormones Metabolism Neurology Oxides Proteins RNA Hypothyroid Mitochondria Mitochondrial complex I Neuronal nitric-oxide synthase Nitric acid 3,3',5' triiodothyronine cyclin D1 liver enzyme messenger RNA mitochondrial complex 1 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase neuronal nitric oxide synthase alpha nitric oxide oxidoreductase peroxynitrite reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thiamazole thyrotropin tyrosine unclassified drug heat shock protein 90 isoprotein nitric oxide synthase oxidizing agent oxygen peroxynitrous acid thyroid hormone animal cell animal experiment animal tissue article basal metabolic rate cell communication cellular distribution controlled study enzyme activity enzyme inactivation enzyme localization hypothyroidism liothyronine blood level male mitochondrial respiration nitration nonhuman oxygen consumption phenotype priority journal protein expression protein transport rat signal transduction animal cell fractionation chemical model chemistry cytosol electron enzymology genetic transcription immunoblotting immunoelectron microscopy immunoprecipitation liver liver mitochondrion metabolism mitochondrion pathology polyacrylamide gel electrophoresis reverse transcription polymerase chain reaction Wistar rat Animals Cyclin D1 Cytosol Electron Transport Complex I Electrons Electrophoresis, Polyacrylamide Gel HSP90 Heat-Shock Proteins Hypothyroidism Immunoblotting Immunoprecipitation Liver Male MAP Kinase Signaling System Microscopy, Immunoelectron Mitochondria, Liver Models, Chemical NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Nitric Oxide Synthase Type I Oxidants Oxygen p38 Mitogen-Activated Protein Kinases Peroxynitrous Acid Phenotype Protein Isoforms Protein Transport Rats Rats, Wistar Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Subcellular Fractions Thyroid Hormones Transcription, Genetic
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00219258_v281_n8_p4779_Franco
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Complexation Hormones Metabolism Neurology Oxides Proteins RNA Hypothyroid Mitochondria Mitochondrial complex I Neuronal nitric-oxide synthase Nitric acid 3,3',5' triiodothyronine cyclin D1 liver enzyme messenger RNA mitochondrial complex 1 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase neuronal nitric oxide synthase alpha nitric oxide oxidoreductase peroxynitrite reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thiamazole thyrotropin tyrosine unclassified drug cyclin D1 heat shock protein 90 isoprotein messenger RNA mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase nitric oxide synthase oxidizing agent oxygen peroxynitrous acid reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thyroid hormone animal cell animal experiment animal tissue article basal metabolic rate cell communication cellular distribution controlled study enzyme activity enzyme inactivation enzyme localization hypothyroidism liothyronine blood level male mitochondrial respiration nitration nonhuman oxygen consumption phenotype priority journal protein expression protein transport rat signal transduction animal cell fractionation chemical model chemistry cytosol electron enzymology genetic transcription hypothyroidism immunoblotting immunoelectron microscopy immunoprecipitation liver liver mitochondrion metabolism mitochondrion pathology polyacrylamide gel electrophoresis reverse transcription polymerase chain reaction Wistar rat Animals Cyclin D1 Cytosol Electron Transport Complex I Electrons Electrophoresis, Polyacrylamide Gel HSP90 Heat-Shock Proteins Hypothyroidism Immunoblotting Immunoprecipitation Liver Male MAP Kinase Signaling System Microscopy, Immunoelectron Mitochondria Mitochondria, Liver Models, Chemical NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Nitric Oxide Synthase Type I Oxidants Oxygen p38 Mitogen-Activated Protein Kinases Peroxynitrous Acid Phenotype Protein Isoforms Protein Transport Rats Rats, Wistar Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Subcellular Fractions Thyroid Hormones Transcription, Genetic
spellingShingle	Complexation Hormones Metabolism Neurology Oxides Proteins RNA Hypothyroid Mitochondria Mitochondrial complex I Neuronal nitric-oxide synthase Nitric acid 3,3',5' triiodothyronine cyclin D1 liver enzyme messenger RNA mitochondrial complex 1 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase neuronal nitric oxide synthase alpha nitric oxide oxidoreductase peroxynitrite reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thiamazole thyrotropin tyrosine unclassified drug cyclin D1 heat shock protein 90 isoprotein messenger RNA mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase nitric oxide synthase oxidizing agent oxygen peroxynitrous acid reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thyroid hormone animal cell animal experiment animal tissue article basal metabolic rate cell communication cellular distribution controlled study enzyme activity enzyme inactivation enzyme localization hypothyroidism liothyronine blood level male mitochondrial respiration nitration nonhuman oxygen consumption phenotype priority journal protein expression protein transport rat signal transduction animal cell fractionation chemical model chemistry cytosol electron enzymology genetic transcription hypothyroidism immunoblotting immunoelectron microscopy immunoprecipitation liver liver mitochondrion metabolism mitochondrion pathology polyacrylamide gel electrophoresis reverse transcription polymerase chain reaction Wistar rat Animals Cyclin D1 Cytosol Electron Transport Complex I Electrons Electrophoresis, Polyacrylamide Gel HSP90 Heat-Shock Proteins Hypothyroidism Immunoblotting Immunoprecipitation Liver Male MAP Kinase Signaling System Microscopy, Immunoelectron Mitochondria Mitochondria, Liver Models, Chemical NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Nitric Oxide Synthase Type I Oxidants Oxygen p38 Mitogen-Activated Protein Kinases Peroxynitrous Acid Phenotype Protein Isoforms Protein Transport Rats Rats, Wistar Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Subcellular Fractions Thyroid Hormones Transcription, Genetic Franco, M.C. Antico Arciuch, V.G. Peralta, J.G. Galli, S. Levisman, D. López, L.M. Romorini, L. Poderoso, J.J. Carreras, M.C. Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase
topic_facet	Complexation Hormones Metabolism Neurology Oxides Proteins RNA Hypothyroid Mitochondria Mitochondrial complex I Neuronal nitric-oxide synthase Nitric acid 3,3',5' triiodothyronine cyclin D1 liver enzyme messenger RNA mitochondrial complex 1 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase neuronal nitric oxide synthase alpha nitric oxide oxidoreductase peroxynitrite reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thiamazole thyrotropin tyrosine unclassified drug cyclin D1 heat shock protein 90 isoprotein messenger RNA mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase nitric oxide synthase oxidizing agent oxygen peroxynitrous acid reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thyroid hormone animal cell animal experiment animal tissue article basal metabolic rate cell communication cellular distribution controlled study enzyme activity enzyme inactivation enzyme localization hypothyroidism liothyronine blood level male mitochondrial respiration nitration nonhuman oxygen consumption phenotype priority journal protein expression protein transport rat signal transduction animal cell fractionation chemical model chemistry cytosol electron enzymology genetic transcription hypothyroidism immunoblotting immunoelectron microscopy immunoprecipitation liver liver mitochondrion metabolism mitochondrion pathology polyacrylamide gel electrophoresis reverse transcription polymerase chain reaction Wistar rat Animals Cyclin D1 Cytosol Electron Transport Complex I Electrons Electrophoresis, Polyacrylamide Gel HSP90 Heat-Shock Proteins Hypothyroidism Immunoblotting Immunoprecipitation Liver Male MAP Kinase Signaling System Microscopy, Immunoelectron Mitochondria Mitochondria, Liver Models, Chemical NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Nitric Oxide Synthase Type I Oxidants Oxygen p38 Mitogen-Activated Protein Kinases Peroxynitrous Acid Phenotype Protein Isoforms Protein Transport Rats Rats, Wistar Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Subcellular Fractions Thyroid Hormones Transcription, Genetic
description	Although transcriptional effects of thyroid hormones have substantial influence on oxidative metabolism, how thyroid sets basal metabolic rate remains obscure. Compartmental localization of nitric-oxide synthases is important for nitric oxide signaling. We therefore examined liver neuronal nitric-oxide synthase-α (nNOS) subcellular distribution as a putative mechanism for thyroid effects on rat metabolic rate. At low 3,3′,5-triiodo-L-thyronine levels, nNOS mRNA increased by 3-fold, protein expression by one-fold, and nNOS was selectively translocated to mitochondria without changes in other isoforms. In contrast, under thyroid hormone administration, mRNA level did not change and nNOS remained predominantly localized in cytosol. In hypothyroidism, nNOS translocation resulted in enhanced mitochondrial nitric-oxide synthase activity with low O2 uptake. In this context, NO utilization increased active O2 species and peroxynitrite yields and tyrosine nitration of complex I proteins that reduced complex activity. Hypothyroidism was also associated to high phospho-p38 mitogen-activated protein kinase and decreased phospho-extracellular signal-regulated kinase 1/2 and cyclin D1 levels. Similarly to thyroid hormones, but without changing thyroid status, nitric-oxide synthase inhibitor Nω-nitro-L-arginine methyl ester increased basal metabolic rate, prevented mitochondrial nitration and complex I derangement, and turned mitogen-activated protein kinase signaling and cyclin D1 expression back to control pattern. We surmise that nNOS spatial confinement in mitochondria is a significant downstream effector of thyroid hormone and hypothyroid phenotype. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
format	JOUR
author	Franco, M.C. Antico Arciuch, V.G. Peralta, J.G. Galli, S. Levisman, D. López, L.M. Romorini, L. Poderoso, J.J. Carreras, M.C.
author_facet	Franco, M.C. Antico Arciuch, V.G. Peralta, J.G. Galli, S. Levisman, D. López, L.M. Romorini, L. Poderoso, J.J. Carreras, M.C.
author_sort	Franco, M.C.
title	Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase
title_short	Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase
title_full	Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase
title_fullStr	Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase
title_full_unstemmed	Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase
title_sort	hypothyroid phenotype is contributed by mitochondrial complex i inactivation due to translocated neuronal nitric-oxide synthase
url	http://hdl.handle.net/20.500.12110/paper_00219258_v281_n8_p4779_Franco
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spelling	todo:paper_00219258_v281_n8_p4779_Franco2023-10-03T14:23:11Z Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase Franco, M.C. Antico Arciuch, V.G. Peralta, J.G. Galli, S. Levisman, D. López, L.M. Romorini, L. Poderoso, J.J. Carreras, M.C. Complexation Hormones Metabolism Neurology Oxides Proteins RNA Hypothyroid Mitochondria Mitochondrial complex I Neuronal nitric-oxide synthase Nitric acid 3,3',5' triiodothyronine cyclin D1 liver enzyme messenger RNA mitochondrial complex 1 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase neuronal nitric oxide synthase alpha nitric oxide oxidoreductase peroxynitrite reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thiamazole thyrotropin tyrosine unclassified drug cyclin D1 heat shock protein 90 isoprotein messenger RNA mitogen activated protein kinase p38 n(g) nitroarginine methyl ester neuronal nitric oxide synthase nitric oxide synthase oxidizing agent oxygen peroxynitrous acid reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) thyroid hormone animal cell animal experiment animal tissue article basal metabolic rate cell communication cellular distribution controlled study enzyme activity enzyme inactivation enzyme localization hypothyroidism liothyronine blood level male mitochondrial respiration nitration nonhuman oxygen consumption phenotype priority journal protein expression protein transport rat signal transduction animal cell fractionation chemical model chemistry cytosol electron enzymology genetic transcription hypothyroidism immunoblotting immunoelectron microscopy immunoprecipitation liver liver mitochondrion metabolism mitochondrion pathology polyacrylamide gel electrophoresis reverse transcription polymerase chain reaction Wistar rat Animals Cyclin D1 Cytosol Electron Transport Complex I Electrons Electrophoresis, Polyacrylamide Gel HSP90 Heat-Shock Proteins Hypothyroidism Immunoblotting Immunoprecipitation Liver Male MAP Kinase Signaling System Microscopy, Immunoelectron Mitochondria Mitochondria, Liver Models, Chemical NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Nitric Oxide Synthase Type I Oxidants Oxygen p38 Mitogen-Activated Protein Kinases Peroxynitrous Acid Phenotype Protein Isoforms Protein Transport Rats Rats, Wistar Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Subcellular Fractions Thyroid Hormones Transcription, Genetic Although transcriptional effects of thyroid hormones have substantial influence on oxidative metabolism, how thyroid sets basal metabolic rate remains obscure. Compartmental localization of nitric-oxide synthases is important for nitric oxide signaling. We therefore examined liver neuronal nitric-oxide synthase-α (nNOS) subcellular distribution as a putative mechanism for thyroid effects on rat metabolic rate. At low 3,3′,5-triiodo-L-thyronine levels, nNOS mRNA increased by 3-fold, protein expression by one-fold, and nNOS was selectively translocated to mitochondria without changes in other isoforms. In contrast, under thyroid hormone administration, mRNA level did not change and nNOS remained predominantly localized in cytosol. In hypothyroidism, nNOS translocation resulted in enhanced mitochondrial nitric-oxide synthase activity with low O2 uptake. In this context, NO utilization increased active O2 species and peroxynitrite yields and tyrosine nitration of complex I proteins that reduced complex activity. Hypothyroidism was also associated to high phospho-p38 mitogen-activated protein kinase and decreased phospho-extracellular signal-regulated kinase 1/2 and cyclin D1 levels. Similarly to thyroid hormones, but without changing thyroid status, nitric-oxide synthase inhibitor Nω-nitro-L-arginine methyl ester increased basal metabolic rate, prevented mitochondrial nitration and complex I derangement, and turned mitogen-activated protein kinase signaling and cyclin D1 expression back to control pattern. We surmise that nNOS spatial confinement in mitochondria is a significant downstream effector of thyroid hormone and hypothyroid phenotype. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc. Fil:Franco, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Antico Arciuch, V.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Galli, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Romorini, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v281_n8_p4779_Franco

Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase

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