Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage
Five-sixths nephrectomy (5/6Nx) model is widely used for studying the mechanisms involved in chronic kidney disease (CKD) progression, a kidney pathology that has increased dramatically in recent years. Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the informa...
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| Veröffentlicht in: | International journal of molecular sciences 2020-09, Vol.21 (18), p.6512 |
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| creator | Aparicio-Trejo, Omar Emiliano Rojas-Morales, Pedro Avila-Rojas, Sabino Hazael León-Contreras, Juan Carlos Hernández-Pando, Rogelio Jiménez-Uribe, Alexis Paulina Prieto-Carrasco, Rodrigo Sánchez-Lozada, Laura Gabriela Pedraza-Chaverri, José Tapia, Edilia |
| description | Five-sixths nephrectomy (5/6Nx) model is widely used for studying the mechanisms involved in chronic kidney disease (CKD) progression, a kidney pathology that has increased dramatically in recent years. Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the information on mitochondrial bioenergetics and redox alterations along a time course in a 5/6Nx model is still limited and in some cases contradictory. Therefore, we performed for the first time a time-course study of mitochondrial alterations by high-resolution respirometry in the 5/6Nx model. Our results show a decrease in mitochondrial β-oxidation at early times, as well as a permanent impairment in adenosine triphosphate (ATP) production in CI-linked respiration, a permanent oxidative state in mitochondria and decoupling of these organelles. These pathological alterations are linked to the early decrease in complex I and ATP synthase activities and to the further decrease in complex III activity. Therefore, our results may suggest that mitochondrial bioenergetics impairment is an early event in renal damage, whose persistence in time aggravates CKD development in the 5/6Nx model. |
| doi_str_mv | 10.3390/ijms21186512 |
| format | Article |
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Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the information on mitochondrial bioenergetics and redox alterations along a time course in a 5/6Nx model is still limited and in some cases contradictory. Therefore, we performed for the first time a time-course study of mitochondrial alterations by high-resolution respirometry in the 5/6Nx model. Our results show a decrease in mitochondrial β-oxidation at early times, as well as a permanent impairment in adenosine triphosphate (ATP) production in CI-linked respiration, a permanent oxidative state in mitochondria and decoupling of these organelles. These pathological alterations are linked to the early decrease in complex I and ATP synthase activities and to the further decrease in complex III activity. Therefore, our results may suggest that mitochondrial bioenergetics impairment is an early event in renal damage, whose persistence in time aggravates CKD development in the 5/6Nx model.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21186512</identifier><identifier>PMID: 32899919</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenosine triphosphate ; Animals ; ATP synthase ; Bioenergetics ; Creatinine ; Decoupling ; Diabetes ; Disease Progression ; Electron transport ; Energy Metabolism ; Hemodynamics ; Hemodynamics - physiology ; Impairment ; Kidney - blood supply ; Kidney - metabolism ; Kidney - pathology ; Kidney - surgery ; Kidney diseases ; Male ; Mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Nephrectomy ; Nephrectomy - adverse effects ; Nephrectomy - methods ; Organelles ; Oxidation ; Oxidation-Reduction ; Oxidative stress ; Oxidative Stress - physiology ; Oxygen Consumption - physiology ; Postoperative Complications - metabolism ; Postoperative Complications - pathology ; Rats ; Rats, Wistar ; Renal Insufficiency, Chronic - etiology ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - pathology ; Respiration ; Respirometry ; Surgery ; Time Factors</subject><ispartof>International journal of molecular sciences, 2020-09, Vol.21 (18), p.6512</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the information on mitochondrial bioenergetics and redox alterations along a time course in a 5/6Nx model is still limited and in some cases contradictory. Therefore, we performed for the first time a time-course study of mitochondrial alterations by high-resolution respirometry in the 5/6Nx model. Our results show a decrease in mitochondrial β-oxidation at early times, as well as a permanent impairment in adenosine triphosphate (ATP) production in CI-linked respiration, a permanent oxidative state in mitochondria and decoupling of these organelles. These pathological alterations are linked to the early decrease in complex I and ATP synthase activities and to the further decrease in complex III activity. Therefore, our results may suggest that mitochondrial bioenergetics impairment is an early event in renal damage, whose persistence in time aggravates CKD development in the 5/6Nx model.</description><subject>Adenosine triphosphate</subject><subject>Animals</subject><subject>ATP synthase</subject><subject>Bioenergetics</subject><subject>Creatinine</subject><subject>Decoupling</subject><subject>Diabetes</subject><subject>Disease Progression</subject><subject>Electron transport</subject><subject>Energy Metabolism</subject><subject>Hemodynamics</subject><subject>Hemodynamics - physiology</subject><subject>Impairment</subject><subject>Kidney - blood supply</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney - surgery</subject><subject>Kidney diseases</subject><subject>Male</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Nephrectomy</subject><subject>Nephrectomy - 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Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the information on mitochondrial bioenergetics and redox alterations along a time course in a 5/6Nx model is still limited and in some cases contradictory. Therefore, we performed for the first time a time-course study of mitochondrial alterations by high-resolution respirometry in the 5/6Nx model. Our results show a decrease in mitochondrial β-oxidation at early times, as well as a permanent impairment in adenosine triphosphate (ATP) production in CI-linked respiration, a permanent oxidative state in mitochondria and decoupling of these organelles. These pathological alterations are linked to the early decrease in complex I and ATP synthase activities and to the further decrease in complex III activity. Therefore, our results may suggest that mitochondrial bioenergetics impairment is an early event in renal damage, whose persistence in time aggravates CKD development in the 5/6Nx model.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32899919</pmid><doi>10.3390/ijms21186512</doi><orcidid>https://orcid.org/0000-0001-6628-4411</orcidid><orcidid>https://orcid.org/0000-0001-8827-1670</orcidid><orcidid>https://orcid.org/0000-0003-0348-9617</orcidid><orcidid>https://orcid.org/0000-0002-1620-0416</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine triphosphate Animals ATP synthase Bioenergetics Creatinine Decoupling Diabetes Disease Progression Electron transport Energy Metabolism Hemodynamics Hemodynamics - physiology Impairment Kidney - blood supply Kidney - metabolism Kidney - pathology Kidney - surgery Kidney diseases Male Mitochondria Mitochondria - metabolism Mitochondria - pathology Nephrectomy Nephrectomy - adverse effects Nephrectomy - methods Organelles Oxidation Oxidation-Reduction Oxidative stress Oxidative Stress - physiology Oxygen Consumption - physiology Postoperative Complications - metabolism Postoperative Complications - pathology Rats Rats, Wistar Renal Insufficiency, Chronic - etiology Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - pathology Respiration Respirometry Surgery Time Factors |
| title | Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage |
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