PMID- 17018880
OWN - NLM
STAT- MEDLINE
DCOM- 20061025
LR  - 20190608
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 231
IP  - 9
DP  - 2006 Oct
TI  - Cytotoxicity of nitric oxide is alleviated by zinc-mediated expression of 
      antioxidant genes.
PG  - 1555-63
AB  - Metallothioneins (MTs) are small, cysteine-rich zinc binding proteins that are 
      powerful antioxidants. In this study, we investigated the interaction between 
      zinc, MTs, and other components of the antioxidant defense system in HepG2 cells. 
      Cells were preincubated with zinc and then exposed to sodium nitroprusside (SNP), 
      a nitric oxide (NO) donor. Both zinc pretreatment and SNP exposure separately 
      induced transcription of MT genes (MT1A, MT2A, MT1E, MT1X), as measured using 
      real time-polymerase chain reaction (PCR) after reverse transcription (RT). 
      Pretreatment of HepG2 cells with zinc sulfate (ZnSO4) followed by SNP exposure 
      caused MT and glucose-6-phosphate dehydrogenase (G6PD) mRNA levels to increase 
      more than in cells only exposed to SNP. However, when cells were incubated with 
      N,N,N',N'-tetrakis(2-pyridylmethyl)ethyl-enediamine (TPEN), a membrane-permeant 
      Zn2+ chelator, the stimulation of MT transcription by SNP was blocked, suggesting 
      that SNP-induced upregulation of these genes is zinc-dependent. Human 
      glutathione-S-transferase (hGSTA1) and G6PD mRNA levels in the cells treated with 
      5 microM TPEN decreased. Additionally, the induction of MT by SNP after zinc 
      pretreatment appears to be mediated by metal-activated transcription factor-1 
      (MTF-1), which is induced by labile zinc in the cytosol. SNP cytotoxicity was 
      inhibited by preincubation with zinc. Taken together, these results suggest that 
      NO plays an important role in regulation of cellular zinc homeostasis and that 
      NO-mediated release of protein-bound Zn2+ may be an important signal in 
      antioxidant defense.
FAU - Chung, Mi Ja
AU  - Chung MJ
AD  - Division of Food Science, College of Life and Environmental Sciences, Institute 
      of Biomedical Sciences and Safety, Korea University, Seoul 136-713, Korea.
FAU - Hogstrand, Christer
AU  - Hogstrand C
FAU - Lee, Sung-Joon
AU  - Lee SJ
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (DNA Primers)
RN  - 0 (Ethylenediamines)
RN  - 0 (Nitric Oxide Donors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9038-94-2 (Metallothionein)
RN  - EC 1.1.1.49 (Glucosephosphate Dehydrogenase)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - J41CSQ7QDS (Zinc)
RN  - R9PTU1U29I (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine)
SB  - IM
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - DNA Primers
MH  - Ethylenediamines/pharmacology
MH  - Glucosephosphate Dehydrogenase/*genetics
MH  - Glutathione Transferase/*genetics
MH  - Humans
MH  - Metallothionein/*genetics
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/*pharmacology
MH  - Nitrosation
MH  - Oxidative Stress
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Zinc/*pharmacology
EDAT- 2006/10/05 09:00
MHDA- 2006/10/26 09:00
CRDT- 2006/10/05 09:00
PHST- 2006/10/05 09:00 [pubmed]
PHST- 2006/10/26 09:00 [medline]
PHST- 2006/10/05 09:00 [entrez]
AID - 231/9/1555 [pii]
AID - 10.1177/153537020623100916 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2006 Oct;231(9):1555-63. doi: 10.1177/153537020623100916.