Biomol Ther.  2018 Mar;26(2):175-181. 10.4062/biomolther.2018.009.

Carbon Monoxide Ameliorates 6-Hydroxydopamine-Induced Cell Death in C6 Glioma Cells

• Moon H
• Jang JH
• Jang TC
• Park GH

• KMID: 2429057
• DOI: http://doi.org/10.4062/biomolther.2018.009

Abstract

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

Keyword

CO; PD; Neuroprotection; Nrf2; HO-1; SOD

MeSH Terms

Blood Vessels
Carbon Monoxide*
Carbon*
Caspase 3
Cell Death*
Glioma*
Heart Arrest
Heart Failure
Heme Oxygenase-1
Liver Failure
Neurodegenerative Diseases
Neuroprotection
Neurotransmitter Agents
NF-E2-Related Factor 2
Oxidopamine
Phosphorylation
Stomach Neoplasms
Superoxides
Transcription Factors
Up-Regulation
Carbon
Carbon Monoxide
Caspase 3
Heme Oxygenase-1
NF-E2-Related Factor 2
Neurotransmitter Agents
Oxidopamine
Superoxides
Transcription Factors