PMID- 7491977
OWN - NLM
STAT- MEDLINE
DCOM- 19960104
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 269
IP  - 5 Pt 1
DP  - 1995 Nov
TI  - Activation of NF-kappa B and elevation of MnSOD gene expression by thiol reducing 
      agents in lung adenocarcinoma (A549) cells.
PG  - L588-602
AB  - The effect of reducing agents, including N-acetylcysteine (NAC), dithiothreitol 
      (DTT), and 2-mercaptoethanol (2-ME) on nuclear transcription factor-kappa B 
      (NF-kappa B) activation and manganese superoxide dismutase (MnSOD) expression was 
      investigated in a pulmonary adenocarcinoma (A549) cell line. NAC, DTT, and 2-ME 
      each activated the transcription factor NF-kappa B and increased steady-state 
      levels of MnSOD mRNA and enzyme activity in these cells. In addition, NAC, DTT, 
      and 2-ME increased chloramphenicol acetyltransferase (CAT) activity in cells 
      transfected with a construct containing the CAT gene under the control of the rat 
      MnSOD promoter. SOD and catalase (500 U/ml) plus ethanol (1 mM) did not inhibit 
      activation of NF-kappa B or elevation of steady-state MnSOD mRNA levels by NAC, 
      DTT, or 2-ME. Controls in which comparable amounts of O2-. to those produced by 
      thiols were generated by hypoxanthine and xanthine oxidase, or in which H2O2 was 
      added directly, had neither activated NF-kappa B nor elevated MnSOD mRNA. This 
      shows that reactive oxygen intermediates, which may be formed during 
      autooxidation, may not contribute to activation of NF-kappa B. Because the MnSOD 
      promoter also contains potential binding sites for other transcription factors, 
      such as promoter-selective transcription factor-1 (SP-1), activator protein-1 
      (AP-1), AP-2, adenosine 3',5'-cyclic monophosphate-regulator element binding 
      factor (CREB), and transcription factor IID complex (TFIID), the effect of thiols 
      on their activation also were evaluated. In contrast to findings with NF-kappa B, 
      there was only minor activation of AP-1 by thiols, and none of the other 
      transcription factors were activated by thiols. AP-1 activation was inhibited by 
      catalase (500 U/ml) plus SOD plus ethanol (1 mM). Addition of 700 microM H2O2 
      also activated AP-1, and catalase at 500 U/ml prevented this activation. This 
      indicates that H2O2 produced as a result of autooxidation of thiols can activate 
      AP-1 but not NF-kappa B. Thus a close association between exposure to reducing 
      agents, activation of NF-kappa B, and elevation of MnSOD gene expression is 
      demonstrated.
FAU - Das, K C
AU  - Das KC
AD  - Department of Pediatrics, National Jewish Center for Immunology and Respiratory 
      Medicine, Denver, Colorado 80206, USA.
FAU - Lewis-Molock, Y
AU  - Lewis-Molock Y
FAU - White, C W
AU  - White CW
LA  - eng
GR  - 1 P50 HL-46481/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Molecular Probes)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Transcription Factor AP-1)
RN  - 60-24-2 (Mercaptoethanol)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - T8ID5YZU6Y (Dithiothreitol)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/metabolism
MH  - Animals
MH  - Base Sequence
MH  - Dithiothreitol/metabolism
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Mercaptoethanol/metabolism
MH  - Molecular Probes/genetics
MH  - Molecular Sequence Data
MH  - NF-kappa B/*physiology
MH  - Oxidation-Reduction
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Sulfhydryl Compounds/metabolism/*pharmacology
MH  - Superoxide Dismutase/*genetics
MH  - Transcription Factor AP-1/physiology
MH  - Tumor Cells, Cultured
EDAT- 1995/11/01 00:00
MHDA- 1995/11/01 00:01
CRDT- 1995/11/01 00:00
PHST- 1995/11/01 00:00 [pubmed]
PHST- 1995/11/01 00:01 [medline]
PHST- 1995/11/01 00:00 [entrez]
AID - 10.1152/ajplung.1995.269.5.L588 [doi]
PST - ppublish
SO  - Am J Physiol. 1995 Nov;269(5 Pt 1):L588-602. doi: 
      10.1152/ajplung.1995.269.5.L588.