Nitric oxide, can it be only good? Increasing the antioxidant properties of nitric oxide in hepatocytes by YC-1 compound

Publication Type

Journal contribution (peer reviewed)

Authors

Aharoni-Simon, M.; Anavi, S.; Beifuss, U.; Madar, Z.; Tirsoh, O.

Year of publication

2012

Published in

Nitric Oxide

Band/Volume

27/

DOI

10.1016/j.niox.2012.08.076,

Page (from - to)

248-256

The aim of the study was to evaluate the effect of Nitric oxide (NO) on redox changes and fat accumulation in hepatocytes. AML-12 hepatocytes were exposed to the NO donor Diethylenetriamine-NONOate (DETA-NO). DETA-NO led to a dose- and time-dependent increase in lipid accumulation in the cells, measured by Nile red fluorescence. Exposure of the cells to 1 mM DETA-NO for 24 h increased reactive oxygen species production, mainly peroxides. At the same time, NO induced elevation of reduced glutathione (GSH) and a mild activation of the antioxidant transcription factors Hypoxia-inducible factor 1a (HIF1a) and NF-E2 related factor 2 (Nrf-2). We used 100 lM YC-1 to inhibit HIF1a activity and induce activation of soluble Guanylate Cyclase (sGC). YC-1 alone did not affect fat accumulation, and only moderately increased the expression of Nrf-2-targeted genes Heme oxygenase 1 (Hmox1), NAD(P)H dehydrogenase (quinone 1) (Nqo1) and Glutathione S-transferase a1 (Gsta1). However, YC-1 abolished the negative effect of NO on fat accumulation when administered together. Strikingly, YC-1 potentiated the effect of NO on Nrf-2 activation, thus increasing dramatically the antioxidant properties of NO. Moreover, YC-1 intensified the effect of NO on the expression of peroxisome-proliferator-activated receptor-gamma co-activator 1a (PGC1a) and mitochondrial biogenesis markers. This study suggests that YC-1 may shift the deleterious effects of NO into the beneficial ones, and may improve the antioxidant properties of NO