PMID- 22955014
OWN - NLM
STAT- MEDLINE
DCOM- 20130626
LR  - 20161125
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Linking)
VI  - 27
IP  - 4
DP  - 2012 Dec 1
TI  - Nitric oxide, can it be only good? Increasing the antioxidant properties of 
      nitric oxide in hepatocytes by YC-1 compound.
PG  - 248-56
LID - S1089-8603(12)00373-4 [pii]
LID - 10.1016/j.niox.2012.08.076 [doi]
AB  - 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 1mM DETA-NO for 24h 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 1alpha (HIF1alpha) and NF-E2 related 
      factor 2 (Nrf-2). We used 100 muM YC-1 to inhibit HIF1alpha 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 alpha1 (Gstalpha1). 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 
      1alpha (PGC1alpha) 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.
CI  - 2012 Elsevier Inc. All rights reserved
FAU - Aharoni-Simon, Michal
AU  - Aharoni-Simon M
AD  - The School of Nutritional Sciences, Institute of Biochemistry, Food Science and 
      Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The 
      Hebrew University of Jerusalem, Rehovot, Israel.
FAU - Anavi, Sarit
AU  - Anavi S
FAU - Beifuss, Uwe
AU  - Beifuss U
FAU - Madar, Zecharia
AU  - Madar Z
FAU - Tirosh, Oren
AU  - Tirosh O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120828
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Antioxidants)
RN  - 0 (Indazoles)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nitroso Compounds)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 146724-94-9 (2,2'-(hydroxynitrosohydrazono)bis-ethanamine)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Glutathione/metabolism
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Hepatocytes/*drug effects/*metabolism
MH  - Humans
MH  - Indazoles/*pharmacology
MH  - Mice
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitroso Compounds/pharmacology
MH  - Transforming Growth Factor alpha/genetics/metabolism
EDAT- 2012/09/08 06:00
MHDA- 2013/06/28 06:00
CRDT- 2012/09/08 06:00
PHST- 2012/03/18 00:00 [received]
PHST- 2012/08/05 00:00 [revised]
PHST- 2012/08/21 00:00 [accepted]
PHST- 2012/09/08 06:00 [entrez]
PHST- 2012/09/08 06:00 [pubmed]
PHST- 2013/06/28 06:00 [medline]
AID - S1089-8603(12)00373-4 [pii]
AID - 10.1016/j.niox.2012.08.076 [doi]
PST - ppublish
SO  - Nitric Oxide. 2012 Dec 1;27(4):248-56. doi: 10.1016/j.niox.2012.08.076. Epub 2012 
      Aug 28.