alexa The activity of NF-kappaB in Swiss 3T3 cells exposed to aqueous extracts of cigarette smoke is dependent on thioredoxin. Toxicol Sci 59:75-81.


Chemotherapy: Open Access

Author(s): Stephan Gebel, Thomas Muller

Abstract Share this page

Multiple studies in vitro have demonstrated that aqueous ex- tracts of mainstream cigarette smoke (CS) [smoke-bubbled phos- phate-buffered saline (PBS)] induce a distinct pattern of stress response in cultured cells, which may be related to the reported pro-inflammatory activities of CS in vitro and in vivo . Nuclear factor k B (NF- k B) is a transcription factor involved in both inflammatory and stress-dependent cell-signaling processes. Here we report on the activity of NF- k B in cells exposed to subcytotoxic concentrations of smoke-bubbled PBS. Using electrophoretic mo- bility shift assay (EMSA) techniques, we observed a decreased DNA binding of NF- k B during the first 2 h of exposure, which was followed by a more than 2-fold increase over controls after 4 to 6 h of exposure. This type of kinetics is not regulated by I k B- a ,as evidenced by the lack of phosphorylation and degradation of I k B- a in CS-treated cells. However, as demonstrated in immuno- coprecipitation experiments, the kinetics of NF- k B DNA binding is strictly paralleled by decreased and increased complex forma- tion between NF- k B and thioredoxin (Trx), the reducing catalyst of Cys-62 of NF- k B subunit p50, the reduced thiol function of which is essential for efficient NF- k B DNA binding. Monitoring the expression of the gene encoding thioredoxin reductase (TrxR), which is required to keep Trx in a functional reduced state, we observed a significant increase in TrxR mRNA after 2 to6hof exposure. Based on the correspondence between the kinetics of NF- k B DNA binding, NF- k B/Trx complex formation, and TrxR expression, along with a lack of I k B- a phosphorylation and deg- radation, these results suggest that the activity of NF- k BinCS- treated cells is subject mainly to a redox-controlled mechanism dependent on the availability of reduced Trx rather than being controlled by its normal regulator, I k B- a .

  • To read the full article Visit
  • Subscription
This article was published in TOXICOLOGICAL SCIENCES and referenced in Chemotherapy: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version