Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells
Acute kidney injury (AKI) represents a common complication in critically ill patients that is associated with increased morbidity and mortality. In a murine AKI model induced by ischemia/reperfusion injury (IRI), we show that glutamine significantly decreases kidney damage and improves kidney functi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-11-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.163161 |
| _version_ | 1797634350236303360 |
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| author | Katharina Thomas Lisa Zondler Nadine Ludwig Marina Kardell Corinna Lüneburg Katharina Henke Sina Mersmann Andreas Margraf Tilmann Spieker Tobias Tekath Ana Velic Richard Holtmeier Juliane Hermann Vera Jankowski Melanie Meersch Dietmar Vestweber Martin Westphal Johannes Roth Michael A. Schäfers John A. Kellum Clifford A. Lowell Jan Rossaint Alexander Zarbock |
| author_facet | Katharina Thomas Lisa Zondler Nadine Ludwig Marina Kardell Corinna Lüneburg Katharina Henke Sina Mersmann Andreas Margraf Tilmann Spieker Tobias Tekath Ana Velic Richard Holtmeier Juliane Hermann Vera Jankowski Melanie Meersch Dietmar Vestweber Martin Westphal Johannes Roth Michael A. Schäfers John A. Kellum Clifford A. Lowell Jan Rossaint Alexander Zarbock |
| author_sort | Katharina Thomas |
| collection | DOAJ |
| description | Acute kidney injury (AKI) represents a common complication in critically ill patients that is associated with increased morbidity and mortality. In a murine AKI model induced by ischemia/reperfusion injury (IRI), we show that glutamine significantly decreases kidney damage and improves kidney function. We demonstrate that glutamine causes transcriptomic and proteomic reprogramming in murine renal tubular epithelial cells (TECs), resulting in decreased epithelial apoptosis, decreased neutrophil recruitment, and improved mitochondrial functionality and respiration provoked by an ameliorated oxidative phosphorylation. We identify the proteins glutamine gamma glutamyltransferase 2 (Tgm2) and apoptosis signal-regulating kinase (Ask1) as the major targets of glutamine in apoptotic signaling. Furthermore, the direct modulation of the Tgm2-HSP70 signalosome and reduced Ask1 activation resulted in decreased JNK activation, leading to diminished mitochondrial intrinsic apoptosis in TECs. Glutamine administration attenuated kidney damage in vivo during AKI and TEC viability in vitro under inflammatory or hypoxic conditions. |
| first_indexed | 2024-03-11T12:06:25Z |
| format | Article |
| id | doaj.art-30ea337b9c5d4c7ea8eab77560c841db |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:25Z |
| publishDate | 2022-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-30ea337b9c5d4c7ea8eab77560c841db2023-11-07T16:24:47ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-11-01721Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cellsKatharina ThomasLisa ZondlerNadine LudwigMarina KardellCorinna LüneburgKatharina HenkeSina MersmannAndreas MargrafTilmann SpiekerTobias TekathAna VelicRichard HoltmeierJuliane HermannVera JankowskiMelanie MeerschDietmar VestweberMartin WestphalJohannes RothMichael A. SchäfersJohn A. KellumClifford A. LowellJan RossaintAlexander ZarbockAcute kidney injury (AKI) represents a common complication in critically ill patients that is associated with increased morbidity and mortality. In a murine AKI model induced by ischemia/reperfusion injury (IRI), we show that glutamine significantly decreases kidney damage and improves kidney function. We demonstrate that glutamine causes transcriptomic and proteomic reprogramming in murine renal tubular epithelial cells (TECs), resulting in decreased epithelial apoptosis, decreased neutrophil recruitment, and improved mitochondrial functionality and respiration provoked by an ameliorated oxidative phosphorylation. We identify the proteins glutamine gamma glutamyltransferase 2 (Tgm2) and apoptosis signal-regulating kinase (Ask1) as the major targets of glutamine in apoptotic signaling. Furthermore, the direct modulation of the Tgm2-HSP70 signalosome and reduced Ask1 activation resulted in decreased JNK activation, leading to diminished mitochondrial intrinsic apoptosis in TECs. Glutamine administration attenuated kidney damage in vivo during AKI and TEC viability in vitro under inflammatory or hypoxic conditions.https://doi.org/10.1172/jci.insight.163161ImmunologyNephrology |
| spellingShingle | Katharina Thomas Lisa Zondler Nadine Ludwig Marina Kardell Corinna Lüneburg Katharina Henke Sina Mersmann Andreas Margraf Tilmann Spieker Tobias Tekath Ana Velic Richard Holtmeier Juliane Hermann Vera Jankowski Melanie Meersch Dietmar Vestweber Martin Westphal Johannes Roth Michael A. Schäfers John A. Kellum Clifford A. Lowell Jan Rossaint Alexander Zarbock Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells JCI Insight Immunology Nephrology |
| title | Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells |
| title_full | Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells |
| title_fullStr | Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells |
| title_full_unstemmed | Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells |
| title_short | Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells |
| title_sort | glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells |
| topic | Immunology Nephrology |
| url | https://doi.org/10.1172/jci.insight.163161 |
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