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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/18/6512 |
id |
doaj-f4f6a0718e5449ac88355a855aa582ab |
---|---|
record_format |
Article |
spelling |
doaj-f4f6a0718e5449ac88355a855aa582ab2020-11-25T03:43:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-01216512651210.3390/ijms21186512Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal DamageOmar Emiliano Aparicio-Trejo0Pedro Rojas-Morales1Sabino Hazael Avila-Rojas2Juan Carlos León-Contreras3Rogelio Hernández-Pando4Alexis Paulina Jiménez-Uribe5Rodrigo Prieto-Carrasco6Laura Gabriela Sánchez-Lozada7José Pedraza-Chaverri8Edilia Tapia9Department of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, MexicoDepartment of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, MexicoDepartment of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition “Salvador Zubirán”, Mexico City 14000, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition “Salvador Zubirán”, Mexico City 14000, MexicoDepartment of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, MexicoDepartment of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, MexicoDepartment of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, MexicoDepartment of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, MexicoDepartment of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, MexicoFive-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.https://www.mdpi.com/1422-0067/21/18/6512chronic kidney disease5/6 nephrectomyβ-oxidation impairmentmitochondrial damage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Omar Emiliano Aparicio-Trejo Pedro Rojas-Morales Sabino Hazael Avila-Rojas Juan Carlos León-Contreras Rogelio Hernández-Pando Alexis Paulina Jiménez-Uribe Rodrigo Prieto-Carrasco Laura Gabriela Sánchez-Lozada José Pedraza-Chaverri Edilia Tapia |
spellingShingle |
Omar Emiliano Aparicio-Trejo Pedro Rojas-Morales Sabino Hazael Avila-Rojas Juan Carlos León-Contreras Rogelio Hernández-Pando Alexis Paulina Jiménez-Uribe Rodrigo Prieto-Carrasco Laura Gabriela Sánchez-Lozada José Pedraza-Chaverri Edilia Tapia Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage International Journal of Molecular Sciences chronic kidney disease 5/6 nephrectomy β-oxidation impairment mitochondrial damage |
author_facet |
Omar Emiliano Aparicio-Trejo Pedro Rojas-Morales Sabino Hazael Avila-Rojas Juan Carlos León-Contreras Rogelio Hernández-Pando Alexis Paulina Jiménez-Uribe Rodrigo Prieto-Carrasco Laura Gabriela Sánchez-Lozada José Pedraza-Chaverri Edilia Tapia |
author_sort |
Omar Emiliano Aparicio-Trejo |
title |
Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage |
title_short |
Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage |
title_full |
Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage |
title_fullStr |
Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage |
title_full_unstemmed |
Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage |
title_sort |
temporal alterations in mitochondrial β-oxidation and oxidative stress aggravate chronic kidney disease development in 5/6 nephrectomy induced renal damage |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-09-01 |
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. |
topic |
chronic kidney disease 5/6 nephrectomy β-oxidation impairment mitochondrial damage |
url |
https://www.mdpi.com/1422-0067/21/18/6512 |
work_keys_str_mv |
AT omaremilianoapariciotrejo temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT pedrorojasmorales temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT sabinohazaelavilarojas temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT juancarlosleoncontreras temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT rogeliohernandezpando temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT alexispaulinajimenezuribe temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT rodrigoprietocarrasco temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT lauragabrielasanchezlozada temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT josepedrazachaverri temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage AT ediliatapia temporalalterationsinmitochondrialboxidationandoxidativestressaggravatechronickidneydiseasedevelopmentin56nephrectomyinducedrenaldamage |
_version_ |
1724519251465732096 |