Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control
Heme Oxygenase-1 (HO-1), a stress- responsive enzyme which catalyzes heme degradation into iron, carbon monoxide, and biliverdin, exerts a neuroprotective role involving many different signaling pathways. In Parkinson disease patients, elevated HO-1 expression levels in astrocytes are involved in an...
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todo:paper_03784274_v295_n_p357_Gorojod2023-10-03T15:32:20Z Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control Gorojod, R.M. Alaimo, A. Porte Alcon, S. Martinez, J.H. Cortina, M.E. Vazquez, E.S. Kotler, M.L. Astroglia Heme Oxygenase-1 Manganese Manganism Mitochondrial quality control Oxidative stress heme oxygenase 1 manganese chloride reactive oxygen metabolite recombinant enzyme recombinant heme oxygenase 1 unclassified drug chloride heme oxygenase 1 HMOX1 protein, human manganese chloride manganese derivative reactive oxygen metabolite animal cell apoptosis Article astrocyte cell damage cell protection controlled study degenerative disease in vitro study macroglia mitochondrial biogenesis mitochondrial quality control mitophagy neuroprotection nonhuman oxidative stress parkinsonism priority journal protein function quality control animal astrocyte chemically induced dose response drug effect enzymology intoxication metabolism mitochondrial dynamics mitochondrion oxidative stress pathology rat signal transduction time factor tumor cell line Animals Apoptosis Astrocytes Cell Line, Tumor Chlorides Dose-Response Relationship, Drug Heme Oxygenase-1 Manganese Compounds Manganese Poisoning Mitochondria Mitochondrial Degradation Mitochondrial Dynamics Oxidative Stress Parkinsonian Disorders Rats Reactive Oxygen Species Signal Transduction Time Factors Heme Oxygenase-1 (HO-1), a stress- responsive enzyme which catalyzes heme degradation into iron, carbon monoxide, and biliverdin, exerts a neuroprotective role involving many different signaling pathways. In Parkinson disease patients, elevated HO-1 expression levels in astrocytes are involved in antioxidant defense. In the present work, employing an in vitro model of Mn2+-induced Parkinsonism in astroglial C6 cells, we investigated the role of HO-1 in both apoptosis and mitochondrial quality control (MQC). HO-1 exerted a protective effect against Mn2+ injury. In fact, HO-1 decreased both intracellular and mitochondrial reactive oxygen species as well as the appearance of apoptotic features. Considering that Mn2+ induces mitochondrial damage and a defective MQC has been implicated in neurodegenerative diseases, we hypothesized that HO-1 could mediate cytoprotection by regulating the MQC processes. Results obtained provide the first evidence that the beneficial effects of HO-1 in astroglial cells are mediated by the maintenance of both mitochondrial fusion/fission and biogenesis/mitophagy balances. Altogether, our data demonstrate a pro-survival function for HO-1 in Mn2+-induced apoptosis that involves the preservation of a proper MQC. These findings point to HO-1 as a new therapeutic target linked to mitochondrial pathophysiology in Manganism and probably Parkinson´s disease. © 2018 JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03784274_v295_n_p357_Gorojod |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Astroglia Heme Oxygenase-1 Manganese Manganism Mitochondrial quality control Oxidative stress heme oxygenase 1 manganese chloride reactive oxygen metabolite recombinant enzyme recombinant heme oxygenase 1 unclassified drug chloride heme oxygenase 1 HMOX1 protein, human manganese chloride manganese derivative reactive oxygen metabolite animal cell apoptosis Article astrocyte cell damage cell protection controlled study degenerative disease in vitro study macroglia mitochondrial biogenesis mitochondrial quality control mitophagy neuroprotection nonhuman oxidative stress parkinsonism priority journal protein function quality control animal astrocyte chemically induced dose response drug effect enzymology intoxication metabolism mitochondrial dynamics mitochondrion oxidative stress pathology rat signal transduction time factor tumor cell line Animals Apoptosis Astrocytes Cell Line, Tumor Chlorides Dose-Response Relationship, Drug Heme Oxygenase-1 Manganese Compounds Manganese Poisoning Mitochondria Mitochondrial Degradation Mitochondrial Dynamics Oxidative Stress Parkinsonian Disorders Rats Reactive Oxygen Species Signal Transduction Time Factors |
spellingShingle |
Astroglia Heme Oxygenase-1 Manganese Manganism Mitochondrial quality control Oxidative stress heme oxygenase 1 manganese chloride reactive oxygen metabolite recombinant enzyme recombinant heme oxygenase 1 unclassified drug chloride heme oxygenase 1 HMOX1 protein, human manganese chloride manganese derivative reactive oxygen metabolite animal cell apoptosis Article astrocyte cell damage cell protection controlled study degenerative disease in vitro study macroglia mitochondrial biogenesis mitochondrial quality control mitophagy neuroprotection nonhuman oxidative stress parkinsonism priority journal protein function quality control animal astrocyte chemically induced dose response drug effect enzymology intoxication metabolism mitochondrial dynamics mitochondrion oxidative stress pathology rat signal transduction time factor tumor cell line Animals Apoptosis Astrocytes Cell Line, Tumor Chlorides Dose-Response Relationship, Drug Heme Oxygenase-1 Manganese Compounds Manganese Poisoning Mitochondria Mitochondrial Degradation Mitochondrial Dynamics Oxidative Stress Parkinsonian Disorders Rats Reactive Oxygen Species Signal Transduction Time Factors Gorojod, R.M. Alaimo, A. Porte Alcon, S. Martinez, J.H. Cortina, M.E. Vazquez, E.S. Kotler, M.L. Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
topic_facet |
Astroglia Heme Oxygenase-1 Manganese Manganism Mitochondrial quality control Oxidative stress heme oxygenase 1 manganese chloride reactive oxygen metabolite recombinant enzyme recombinant heme oxygenase 1 unclassified drug chloride heme oxygenase 1 HMOX1 protein, human manganese chloride manganese derivative reactive oxygen metabolite animal cell apoptosis Article astrocyte cell damage cell protection controlled study degenerative disease in vitro study macroglia mitochondrial biogenesis mitochondrial quality control mitophagy neuroprotection nonhuman oxidative stress parkinsonism priority journal protein function quality control animal astrocyte chemically induced dose response drug effect enzymology intoxication metabolism mitochondrial dynamics mitochondrion oxidative stress pathology rat signal transduction time factor tumor cell line Animals Apoptosis Astrocytes Cell Line, Tumor Chlorides Dose-Response Relationship, Drug Heme Oxygenase-1 Manganese Compounds Manganese Poisoning Mitochondria Mitochondrial Degradation Mitochondrial Dynamics Oxidative Stress Parkinsonian Disorders Rats Reactive Oxygen Species Signal Transduction Time Factors |
description |
Heme Oxygenase-1 (HO-1), a stress- responsive enzyme which catalyzes heme degradation into iron, carbon monoxide, and biliverdin, exerts a neuroprotective role involving many different signaling pathways. In Parkinson disease patients, elevated HO-1 expression levels in astrocytes are involved in antioxidant defense. In the present work, employing an in vitro model of Mn2+-induced Parkinsonism in astroglial C6 cells, we investigated the role of HO-1 in both apoptosis and mitochondrial quality control (MQC). HO-1 exerted a protective effect against Mn2+ injury. In fact, HO-1 decreased both intracellular and mitochondrial reactive oxygen species as well as the appearance of apoptotic features. Considering that Mn2+ induces mitochondrial damage and a defective MQC has been implicated in neurodegenerative diseases, we hypothesized that HO-1 could mediate cytoprotection by regulating the MQC processes. Results obtained provide the first evidence that the beneficial effects of HO-1 in astroglial cells are mediated by the maintenance of both mitochondrial fusion/fission and biogenesis/mitophagy balances. Altogether, our data demonstrate a pro-survival function for HO-1 in Mn2+-induced apoptosis that involves the preservation of a proper MQC. These findings point to HO-1 as a new therapeutic target linked to mitochondrial pathophysiology in Manganism and probably Parkinson´s disease. © 2018 |
format |
JOUR |
author |
Gorojod, R.M. Alaimo, A. Porte Alcon, S. Martinez, J.H. Cortina, M.E. Vazquez, E.S. Kotler, M.L. |
author_facet |
Gorojod, R.M. Alaimo, A. Porte Alcon, S. Martinez, J.H. Cortina, M.E. Vazquez, E.S. Kotler, M.L. |
author_sort |
Gorojod, R.M. |
title |
Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
title_short |
Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
title_full |
Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
title_fullStr |
Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
title_full_unstemmed |
Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
title_sort |
heme oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
url |
http://hdl.handle.net/20.500.12110/paper_03784274_v295_n_p357_Gorojod |
work_keys_str_mv |
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