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ResearchIn-Press PreviewImmunologyNephrology Open Access | 10.1172/jci.insight.163161

Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells

Katharina Thomas,1 Lisa Zondler,1 Nadine Ludwig,1 Marina Kardell,1 Corinna Lüneburg,1 Katharina Henke,1 Sina Mersmann,1 Andreas Margraf,1 Tilmann Spieker,3 Tobias Tekath,4 Ana Velic,5 Richard Holtmeier,6 Juliane Hermann,7 Vera Jankowski,7 Melanie Meersch,8 Dietmar Vestweber,9 Martin Westphal,10 Johannes Roth,11 Michael A. Schaefers,12 John A. Kellum,13 Clifford A. Lowell,14 Jan Rossaint,15 and Alexander Zarbock15

1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

Find articles by Kardell, M. in: PubMed | Google Scholar |

1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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1Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany

2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Munich, Germany

3Institute for Pathology, St. Franziskus Hospital Muenster, Muenster, Germany

4Institute of Medical Informatics, University of Muenster, Muenster, Germany

5Department of Quantitative Proteomics, University of Tübingen, Tübingen, Germany

6Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany

7Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany

8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

9Department of Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany

10R&D, Fresenius Kabi AG, Bad Hombug, Germany

11Institute of Immunology, University of Münster, Muenster, Germany

12European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany

13Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America

14Department of Laboratory Medicine, UCSF, San Francisco, United States of America

15Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany

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Published September 15, 2022 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.163161.
Copyright © 2022, Thomas et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 15, 2022 - Version history
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Abstract

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, 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 result 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.

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  • Version 1 (September 15, 2022): In-Press Preview
  • Version 2 (November 8, 2022): Electronic publication
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