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

Michal Aharoni-Simon, Sarit Anavi, Uwe Beifuss, Zecharia Madar, Oren Tirosh

Research output: Contribution to journalArticlepeer-review

Abstract

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 1α (HIF1α) and NF-E2 related factor 2 (Nrf-2). We used 100 μM YC-1 to inhibit HIF1α 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 α1 (Gstα1). 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 1α (PGC1α) 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.

Original languageAmerican English
Pages (from-to)248-256
Number of pages9
JournalNitric Oxide - Biology and Chemistry
Volume27
Issue number4
DOIs
StatePublished - 1 Dec 2012

Keywords

  • Fat accumulation
  • HIF1α
  • Hepatocytes
  • Nitric oxide
  • Nrf-2

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Cancer Research
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of 'Nitric oxide, can it be only good? Increasing the antioxidant properties of nitric oxide in hepatocytes by YC-1 compound'. Together they form a unique fingerprint.

Cite this