INVESTIGADORES
VAZQUEZ Elba Susana
artículos
Título:
Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control
Autor/es:
GOROJOD, ROXANA MAYRA; ALAIMO, AGUSTINA; PORTE ALCON, SOLEDAD; MARTINEZ, JIMENA HEBE; CORTINA, MARÍA EUGENIA; VAZQUEZ, ELBA SUSANA; KOTLER, MÓNICA LIDIA
Revista:
TOXICOLOGY LETTERS
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Año: 2018 vol. 295 p. 357 - 368
ISSN:
0378-4274
Resumen:
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.