RGD Reference Report - beta-Carotene and cigarette smoke condensate regulate heme oxygenase-1 and its repressor factor Bach1: relationship with cell growth. - Rat Genome Database

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beta-Carotene and cigarette smoke condensate regulate heme oxygenase-1 and its repressor factor Bach1: relationship with cell growth.

Authors: Palozza, P  Serini, S  Curro, D  Calviello, G  Igarashi, K  Mancuso, C 
Citation: Palozza P, etal., Antioxid Redox Signal. 2006 May-Jun;8(5-6):1069-80.
RGD ID: 2326085
Pubmed: PMID:16771696   (View Abstract at PubMed)
DOI: DOI:10.1089/ars.2006.8.1069   (Journal Full-text)

It has been reported that beta-carotene is able to increase lung cancer risk in chronic smokers, but the mechanism for this association remains unknown. This article reports the first evidence that beta-carotene, combined with cigarette smoke condensate (TAR), regulates heme oxygenase-1 (HO-1) via its transcriptional factor Bach1 and modulates cell growth. Both immortalized rat fibroblasts (RAT-1) and human lung cancer cells (Mv1Lu) exposed to TAR (25 microg/ml), exhibited an initial (6 h) induction of HO-1, followed by a late (24 h) repression due to the activation of Bach1. Heme oxygenase-1 repression was much more consistent when TAR was administered in combination with beta-carotene (1 microM) for 24 h; at this concentration the carotenoid per se did not have any effect on HO-1. Interestingly, the HO-1 repression following TAR plus beta-carotene treatment caused a resynchronization of RAT-1 cell-cycle with a significant increase in the S-phase, and this was probably due to the decreased intracellular levels of carbon monoxide and bilirubin, both of which have antiproliferative effects. The role of HO-1 repression in increasing cell growth was also confirmed in Mv1Lu cells by the "knock down" of the Bach1 gene, thus demonstrating as HO-1 repression is a conserved mechanism by which cells can react to oxidative stress.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to vitamin  IEP 2326085 RGD 
negative regulation of cell population proliferation  IDA 2326085 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Brip1  (BRCA1 interacting helicase 1)


Additional Information