期刊
TOXICOLOGY LETTERS
卷 295, 期 -, 页码 357-368出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.07.045
关键词
Heme Oxygenase-1; Mitochondrial quality control; Oxidative stress; Astroglia; Manganese; Manganism
类别
资金
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET PIP) [5406, 0771]
- CONICET
- Bunge and Born scholarship
Heme Oxygenase-1 (H0-1), 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.
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