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Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration

Serum tyrosine levels increase during aging, neurocognitive, metabolic, and cardiovascular disorders. However, calorie restriction (CR) and sleep lower serum tyrosine levels. We previously showed that tyrosine inhibits tyrosyl-tRNA synthetase (TyrRS)-mediated activation of poly-ADP-ribose polymerase...

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Autores principales: Jhanji, Megha, Rao, Chintada Nageswara, Massey, Jacob C., Hope, Marion C., Zhou, Xueyan, Keene, C. Dirk, Ma, Tao, Wyatt, Michael D., Stewart, Jason A., Sajish, Mathew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187644/
https://www.ncbi.nlm.nih.gov/pubmed/35688816
http://dx.doi.org/10.1038/s41467-022-30785-8
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author Jhanji, Megha
Rao, Chintada Nageswara
Massey, Jacob C.
Hope, Marion C.
Zhou, Xueyan
Keene, C. Dirk
Ma, Tao
Wyatt, Michael D.
Stewart, Jason A.
Sajish, Mathew
author_facet Jhanji, Megha
Rao, Chintada Nageswara
Massey, Jacob C.
Hope, Marion C.
Zhou, Xueyan
Keene, C. Dirk
Ma, Tao
Wyatt, Michael D.
Stewart, Jason A.
Sajish, Mathew
author_sort Jhanji, Megha
collection PubMed
description Serum tyrosine levels increase during aging, neurocognitive, metabolic, and cardiovascular disorders. However, calorie restriction (CR) and sleep lower serum tyrosine levels. We previously showed that tyrosine inhibits tyrosyl-tRNA synthetase (TyrRS)-mediated activation of poly-ADP-ribose polymerase 1 (PARP1). Here, we show that histone serine-ADP-ribosylation is decreased in Alzheimer’s Disease (AD) brains, and increased tyrosine levels deplete TyrRS and cause neuronal DNA damage. However, dopamine and brain-derived neurotrophic factor (BDNF) increase TyrRS and histone serine-ADP-ribosylation. Furthermore, cis-resveratrol (cis-RSV) that binds to TyrRS mimicking a ‘tyrosine-free’ conformation increases TyrRS, facilitates histone serine-ADP-ribosylation-dependent DNA repair, and provides neuroprotection in a TyrRS-dependent manner. Conversely, trans-RSV that binds to TyrRS mimicking a ‘tyrosine-like’ conformation decreases TyrRS, inhibits serine-ADP-ribosylation-dependent DNA repair, and induces neurodegeneration in rat cortical neurons. Our findings suggest that age-associated increase in serum tyrosine levels may effect neurocognitive and metabolic disorders and offer a plausible explanation for divergent results obtained in clinical trials using resveratrol.
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spelling pubmed-91876442022-06-12 Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration Jhanji, Megha Rao, Chintada Nageswara Massey, Jacob C. Hope, Marion C. Zhou, Xueyan Keene, C. Dirk Ma, Tao Wyatt, Michael D. Stewart, Jason A. Sajish, Mathew Nat Commun Article Serum tyrosine levels increase during aging, neurocognitive, metabolic, and cardiovascular disorders. However, calorie restriction (CR) and sleep lower serum tyrosine levels. We previously showed that tyrosine inhibits tyrosyl-tRNA synthetase (TyrRS)-mediated activation of poly-ADP-ribose polymerase 1 (PARP1). Here, we show that histone serine-ADP-ribosylation is decreased in Alzheimer’s Disease (AD) brains, and increased tyrosine levels deplete TyrRS and cause neuronal DNA damage. However, dopamine and brain-derived neurotrophic factor (BDNF) increase TyrRS and histone serine-ADP-ribosylation. Furthermore, cis-resveratrol (cis-RSV) that binds to TyrRS mimicking a ‘tyrosine-free’ conformation increases TyrRS, facilitates histone serine-ADP-ribosylation-dependent DNA repair, and provides neuroprotection in a TyrRS-dependent manner. Conversely, trans-RSV that binds to TyrRS mimicking a ‘tyrosine-like’ conformation decreases TyrRS, inhibits serine-ADP-ribosylation-dependent DNA repair, and induces neurodegeneration in rat cortical neurons. Our findings suggest that age-associated increase in serum tyrosine levels may effect neurocognitive and metabolic disorders and offer a plausible explanation for divergent results obtained in clinical trials using resveratrol. Nature Publishing Group UK 2022-06-10 /pmc/articles/PMC9187644/ /pubmed/35688816 http://dx.doi.org/10.1038/s41467-022-30785-8 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jhanji, Megha
Rao, Chintada Nageswara
Massey, Jacob C.
Hope, Marion C.
Zhou, Xueyan
Keene, C. Dirk
Ma, Tao
Wyatt, Michael D.
Stewart, Jason A.
Sajish, Mathew
Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration
title Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration
title_full Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration
title_fullStr Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration
title_full_unstemmed Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration
title_short Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration
title_sort cis- and trans-resveratrol have opposite effects on histone serine-adp-ribosylation and tyrosine induced neurodegeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187644/
https://www.ncbi.nlm.nih.gov/pubmed/35688816
http://dx.doi.org/10.1038/s41467-022-30785-8
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