Abstract:
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
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Documento: |
Artículo
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Título: | Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control |
Autor: | Gorojod, R.M.; Alaimo, A.; Porte Alcon, S.; Martinez, J.H.; Cortina, M.E.; Vazquez, E.S.; Kotler, M.L. |
Filiación: | CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina. Buenos Aires, Argentina CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica (CM1), Laboratorio Interdisciplinario de Dinámica Celular y Nanoherramientas. Buenos Aires, Argentina CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica (CM1), Laboratorio de Inflamación y Cáncer. Buenos Aires, Argentina CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica (CM1), Laboratorio Interdisciplinario de Dinámica Celular y Nanoherramientas. Buenos Aires, Argentina
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Palabras clave: | 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 |
Año: | 2018
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Volumen: | 295
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Página de inicio: | 357
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Página de fin: | 368
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DOI: |
http://dx.doi.org/10.1016/j.toxlet.2018.07.045 |
Título revista: | Toxicology Letters
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Título revista abreviado: | Toxicol. Lett.
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ISSN: | 03784274
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CODEN: | TOLED
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CAS: | manganese chloride, 11132-78-8, 7773-01-5; chloride, 16887-00-6; Chlorides; Heme Oxygenase-1; HMOX1 protein, human; manganese chloride; Manganese Compounds; Reactive Oxygen Species
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v295_n_p357_Gorojod |
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Citas:
---------- APA ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S. & Kotler, M.L.
(2018)
. Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control. Toxicology Letters, 295, 357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045---------- CHICAGO ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S., et al.
"Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control"
. Toxicology Letters 295
(2018) : 357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045---------- MLA ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S., et al.
"Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control"
. Toxicology Letters, vol. 295, 2018, pp. 357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045---------- VANCOUVER ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S., et al. Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control. Toxicol. Lett. 2018;295:357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045