Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency
Summary: Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a−/− mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteo...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000640 |
| _version_ | 1797903376535519232 |
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| author | Aaron E. Robinson Aleksandra Binek Komal Ramani Niveda Sundararaman Lucía Barbier-Torres Ben Murray Vidya Venkatraman Simion Kreimer Angela Mc Ardle Mazen Noureddin David Fernández-Ramos Fernando Lopitz-Otsoa Virginia Gutiérrez de Juan Oscar Millet José M. Mato Shelly C. Lu Jennifer E. Van Eyk |
| author_facet | Aaron E. Robinson Aleksandra Binek Komal Ramani Niveda Sundararaman Lucía Barbier-Torres Ben Murray Vidya Venkatraman Simion Kreimer Angela Mc Ardle Mazen Noureddin David Fernández-Ramos Fernando Lopitz-Otsoa Virginia Gutiérrez de Juan Oscar Millet José M. Mato Shelly C. Lu Jennifer E. Van Eyk |
| author_sort | Aaron E. Robinson |
| collection | DOAJ |
| description | Summary: Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a−/− mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH Mat1a−/− mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD). Mitochondrial and peroxisomal lipid metabolism proteins were altered in pre-disease mice and persisted in NASH Mat1a−/− mice, which exhibited more progressive alterations in cytoplasmic ribosomes, ER, and nuclear proteins. A common mechanism found in both pre-disease and NASH livers was a hyperphosphorylation signature consistent with casein kinase 2α (CK2α) and AKT1 activation, which was normalized by SAMe administration. This was mimicked in human NAFLD with a metabolomic signature (M-subtype) resembling Mat1a−/− mice. In conclusion, we have identified a common proteome/phosphoproteome signature between Mat1a−/− mice and human NAFLD M-subtype that may have pathophysiological and therapeutic implications. |
| first_indexed | 2024-04-10T09:31:55Z |
| format | Article |
| id | doaj.art-5a0db57b521d4dd29148c78a30164d06 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:55Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5a0db57b521d4dd29148c78a30164d062023-02-19T04:26:50ZengElsevieriScience2589-00422023-02-01262105987Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiencyAaron E. Robinson0Aleksandra Binek1Komal Ramani2Niveda Sundararaman3Lucía Barbier-Torres4Ben Murray5Vidya Venkatraman6Simion Kreimer7Angela Mc Ardle8Mazen Noureddin9David Fernández-Ramos10Fernando Lopitz-Otsoa11Virginia Gutiérrez de Juan12Oscar Millet13José M. Mato14Shelly C. Lu15Jennifer E. Van Eyk16Advanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USAKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building, Room 2097, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USAKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building, Room 2097, Los Angeles, CA 90048, USAKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building, Room 2097, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USAKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building, Room 2097, Los Angeles, CA 90048, USACIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainCIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainCIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainCIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainCIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building, Room 2097, Los Angeles, CA 90048, USA; Corresponding authorAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Blvd, Room 9302, Los Angeles, CA 90048, USA; Corresponding authorSummary: Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a−/− mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH Mat1a−/− mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD). Mitochondrial and peroxisomal lipid metabolism proteins were altered in pre-disease mice and persisted in NASH Mat1a−/− mice, which exhibited more progressive alterations in cytoplasmic ribosomes, ER, and nuclear proteins. A common mechanism found in both pre-disease and NASH livers was a hyperphosphorylation signature consistent with casein kinase 2α (CK2α) and AKT1 activation, which was normalized by SAMe administration. This was mimicked in human NAFLD with a metabolomic signature (M-subtype) resembling Mat1a−/− mice. In conclusion, we have identified a common proteome/phosphoproteome signature between Mat1a−/− mice and human NAFLD M-subtype that may have pathophysiological and therapeutic implications.http://www.sciencedirect.com/science/article/pii/S2589004223000640Human metabolismMolecular biologyProteomics |
| spellingShingle | Aaron E. Robinson Aleksandra Binek Komal Ramani Niveda Sundararaman Lucía Barbier-Torres Ben Murray Vidya Venkatraman Simion Kreimer Angela Mc Ardle Mazen Noureddin David Fernández-Ramos Fernando Lopitz-Otsoa Virginia Gutiérrez de Juan Oscar Millet José M. Mato Shelly C. Lu Jennifer E. Van Eyk Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency iScience Human metabolism Molecular biology Proteomics |
| title | Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency |
| title_full | Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency |
| title_fullStr | Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency |
| title_full_unstemmed | Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency |
| title_short | Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency |
| title_sort | hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in s adenosylmethionine deficiency |
| topic | Human metabolism Molecular biology Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000640 |
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