Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence
Ischemia-reperfusion injury is the leading cause of acute kidney injury. Reactive oxygen species (ROS) production causes cell death or senescence. In cultures of primary human renal tubular epithelial cells (RPTECs) subjected to anoxia-reoxygenation, inhibition of the Krebs cycle at the level of mal...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/10/1415 |
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| author | Theodoros Eleftheriadis Georgios Pissas Spyridon Golfinopoulos Maria Efthymiadi Vassilios Liakopoulos Ioannis Stefanidis |
| author_facet | Theodoros Eleftheriadis Georgios Pissas Spyridon Golfinopoulos Maria Efthymiadi Vassilios Liakopoulos Ioannis Stefanidis |
| author_sort | Theodoros Eleftheriadis |
| collection | DOAJ |
| description | Ischemia-reperfusion injury is the leading cause of acute kidney injury. Reactive oxygen species (ROS) production causes cell death or senescence. In cultures of primary human renal tubular epithelial cells (RPTECs) subjected to anoxia-reoxygenation, inhibition of the Krebs cycle at the level of malate dehydrogenase-2 (MDH-2) decreases hypoxia-inducible factor-1α and oxidative stress and protects from apoptotic or ferroptotic cell death. Inhibition of MDH-2 decreased reoxygenation-induced upregulation of p53 and p21, restored the levels of the proliferation marker Ki-67, and prevented the upregulation of the senescence marker beta-galactosidase and interleukin-1β production. MDH-2 inhibition reduced the reoxygenation-induced upregulation of ATP, but the alterations of critical cell metabolism enzymes allowed enough ATP production to prevent cell energy collapse. Thus, inhibition of the Krebs cycle at the level of MDH-2 protects RPTECs from anoxia-reoxygenation-induced death or senescence. MDH-2 may be a promising pharmaceutical target against ischemia-reperfusion injury. |
| first_indexed | 2024-03-09T20:37:07Z |
| format | Article |
| id | doaj.art-928d5d4fd0a5405099c68dfa75c460ec |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:37:07Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-928d5d4fd0a5405099c68dfa75c460ec2023-11-23T23:08:18ZengMDPI AGBiomolecules2218-273X2022-10-011210141510.3390/biom12101415Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or SenescenceTheodoros Eleftheriadis0Georgios Pissas1Spyridon Golfinopoulos2Maria Efthymiadi3Vassilios Liakopoulos4Ioannis Stefanidis5Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceIschemia-reperfusion injury is the leading cause of acute kidney injury. Reactive oxygen species (ROS) production causes cell death or senescence. In cultures of primary human renal tubular epithelial cells (RPTECs) subjected to anoxia-reoxygenation, inhibition of the Krebs cycle at the level of malate dehydrogenase-2 (MDH-2) decreases hypoxia-inducible factor-1α and oxidative stress and protects from apoptotic or ferroptotic cell death. Inhibition of MDH-2 decreased reoxygenation-induced upregulation of p53 and p21, restored the levels of the proliferation marker Ki-67, and prevented the upregulation of the senescence marker beta-galactosidase and interleukin-1β production. MDH-2 inhibition reduced the reoxygenation-induced upregulation of ATP, but the alterations of critical cell metabolism enzymes allowed enough ATP production to prevent cell energy collapse. Thus, inhibition of the Krebs cycle at the level of MDH-2 protects RPTECs from anoxia-reoxygenation-induced death or senescence. MDH-2 may be a promising pharmaceutical target against ischemia-reperfusion injury.https://www.mdpi.com/2218-273X/12/10/1415ischemia-reperfusion injuryapoptosisferroptosissenescenceKrebs cyclemalate dehydrogenase |
| spellingShingle | Theodoros Eleftheriadis Georgios Pissas Spyridon Golfinopoulos Maria Efthymiadi Vassilios Liakopoulos Ioannis Stefanidis Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence Biomolecules ischemia-reperfusion injury apoptosis ferroptosis senescence Krebs cycle malate dehydrogenase |
| title | Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence |
| title_full | Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence |
| title_fullStr | Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence |
| title_full_unstemmed | Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence |
| title_short | Inhibition of Malate Dehydrogenase-2 Protects Renal Tubular Epithelial Cells from Anoxia-Reoxygenation-Induced Death or Senescence |
| title_sort | inhibition of malate dehydrogenase 2 protects renal tubular epithelial cells from anoxia reoxygenation induced death or senescence |
| topic | ischemia-reperfusion injury apoptosis ferroptosis senescence Krebs cycle malate dehydrogenase |
| url | https://www.mdpi.com/2218-273X/12/10/1415 |
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