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Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys

While urine-based liquid biopsy has expanded to the analyses of extracellular nucleic acids, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles has not been explored as a new class of urine biomarkers for kidney injury. Using rat kidney and mouse tubular cell injury mode...

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Autores principales: Lee, Hee Kyung, Lee, Byung Rho, Lee, Tae Jin, Lee, Chang Min, Li, Chenglong, O’Connor, Paul M., Dong, Zheng, Kwon, Sang-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803936/
https://www.ncbi.nlm.nih.gov/pubmed/35102218
http://dx.doi.org/10.1038/s41598-022-05648-3
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author Lee, Hee Kyung
Lee, Byung Rho
Lee, Tae Jin
Lee, Chang Min
Li, Chenglong
O’Connor, Paul M.
Dong, Zheng
Kwon, Sang-Ho
author_facet Lee, Hee Kyung
Lee, Byung Rho
Lee, Tae Jin
Lee, Chang Min
Li, Chenglong
O’Connor, Paul M.
Dong, Zheng
Kwon, Sang-Ho
author_sort Lee, Hee Kyung
collection PubMed
description While urine-based liquid biopsy has expanded to the analyses of extracellular nucleic acids, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles has not been explored as a new class of urine biomarkers for kidney injury. Using rat kidney and mouse tubular cell injury models, we tested if extracellular vesicle-loaded tRNA and their m(1)A (N(1)-methyladenosine) modification reflect oxidative stress of kidney injury and determined the mechanism of tRNA packaging into extracellular vesicles. We determined a set of extracellular vesicle-loaded, isoaccepting tRNAs differentially released after ischemia–reperfusion injury and oxidative stress. Next, we found that m(1)A modification of extracellular vesicle tRNAs, despite an increase of the methylated tRNAs in intracellular vesicles, showed little or no change under oxidative stress. Mechanistically, oxidative stress decreases tRNA loading into intracellular vesicles while the tRNA-loaded vesicles are accumulated due to decreased release of the vesicles from the cell surface. Furthermore, Maf1-mediated transcriptional repression of the tRNAs decreases the cargo availability for extracellular vesicle release in response to oxidative stress. Taken together, our data support that release of extracellular vesicle tRNAs reflects oxidative stress of kidney tubules which might be useful to detect ischemic kidney injury and could lead to rebalance protein translation under oxidative stress.
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spelling pubmed-88039362022-02-01 Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys Lee, Hee Kyung Lee, Byung Rho Lee, Tae Jin Lee, Chang Min Li, Chenglong O’Connor, Paul M. Dong, Zheng Kwon, Sang-Ho Sci Rep Article While urine-based liquid biopsy has expanded to the analyses of extracellular nucleic acids, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles has not been explored as a new class of urine biomarkers for kidney injury. Using rat kidney and mouse tubular cell injury models, we tested if extracellular vesicle-loaded tRNA and their m(1)A (N(1)-methyladenosine) modification reflect oxidative stress of kidney injury and determined the mechanism of tRNA packaging into extracellular vesicles. We determined a set of extracellular vesicle-loaded, isoaccepting tRNAs differentially released after ischemia–reperfusion injury and oxidative stress. Next, we found that m(1)A modification of extracellular vesicle tRNAs, despite an increase of the methylated tRNAs in intracellular vesicles, showed little or no change under oxidative stress. Mechanistically, oxidative stress decreases tRNA loading into intracellular vesicles while the tRNA-loaded vesicles are accumulated due to decreased release of the vesicles from the cell surface. Furthermore, Maf1-mediated transcriptional repression of the tRNAs decreases the cargo availability for extracellular vesicle release in response to oxidative stress. Taken together, our data support that release of extracellular vesicle tRNAs reflects oxidative stress of kidney tubules which might be useful to detect ischemic kidney injury and could lead to rebalance protein translation under oxidative stress. Nature Publishing Group UK 2022-01-31 /pmc/articles/PMC8803936/ /pubmed/35102218 http://dx.doi.org/10.1038/s41598-022-05648-3 Text en © The Author(s) 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lee, Hee Kyung
Lee, Byung Rho
Lee, Tae Jin
Lee, Chang Min
Li, Chenglong
O’Connor, Paul M.
Dong, Zheng
Kwon, Sang-Ho
Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
title Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
title_full Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
title_fullStr Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
title_full_unstemmed Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
title_short Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
title_sort differential release of extracellular vesicle trna from oxidative stressed renal cells and ischemic kidneys
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803936/
https://www.ncbi.nlm.nih.gov/pubmed/35102218
http://dx.doi.org/10.1038/s41598-022-05648-3
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