Retinoid Signaling and Activator Protein-1 Expression in Ferrets Given  -Carotene Supplements and Exposed to Tobacco Smoke

Wang, Xiangdong; Liu, Chun; Bronson, Roderick T.; Smith, Donald E.; Krinsky, Norman I.; Russell, Robert M.

doi:10.1093/jnci/91.1.60

Cited by 330 publications

(199 citation statements)

References 33 publications

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“…8Ј, 10Ј, 12Ј, 14Ј) are found in the plasma of humans (12) and experimental animals (13) and that these are increased under conditions of oxidative stress and high dietary doses of ␤-carotene (24). We have also found that all of these ␤-apocarotenals and, specifically, ␤-apo-13-carotenone are present in fresh cantaloupe and orange-fleshed melons (11); thus, these compounds may be absorbed directly from the diet.…”

Section: ␤-Apocarotenoids Bind To Ligand-binding Site Of Rars Withmentioning

confidence: 86%

“…It was apparent that the doses of ␤-carotene used in the trial (30 mg/day) were much higher than the range of normal dietary intakes associated with a decreased risk of disease in the observational studies (25). The possible mechanisms involved were explored in elegant studies employing a novel animal model, the smoking ferret (24,28). These studies revealed that under conditions of high dietary ␤-carotene and the oxidative stress of smoking, there was a clear increase in preneoplastic lung cancer lesions in the animals.…”

Section: ␤-Apocarotenoids Bind To Ligand-binding Site Of Rars Withmentioning

confidence: 99%

See 1 more Smart Citation

Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors

Eroglu

Hruszkewycz

Seña

et al. 2012

Journal of Biological Chemistry

126

117

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Section: ␤-Apocarotenoids Bind To Ligand-binding Site Of Rars Withmentioning

confidence: 86%

Section: ␤-Apocarotenoids Bind To Ligand-binding Site Of Rars Withmentioning

confidence: 99%

Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors

Eroglu

Hruszkewycz

Seña

et al. 2012

Journal of Biological Chemistry

126

117

View full text Add to dashboard Cite

“…A study using animal model has demonstrated that cigarette smoke downregulated RAR-b 2 expression but not RAR-a or RAR-g in ferrets compared to the control animals and meanwhile, AP-1 expression was significantly upregulated in the ferrets exposed to cigarette smoke compared to the controls (Wang et al, 1999). A study by another group also showed that nuclear retinoid receptors were potent inhibitors of AP-1 activity generated by either c-Jun homodimers or c-Jun/c-Fos heterodimers (Yang-Yen et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

et al. 2005

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Benzo [a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke and environmental pollution) has been shown to suppress retinoic acid receptor-beta2 (RAR-b 2 ) and induce cyclooxygenase-2 (COX-2) expression. Restoration of RAR-b 2 inhibited growth and colony formation of esophageal cancer cells, which was correlated with COX-2 suppression. In this study, we investigated the molecular mechanisms for RAR-b 2 -mediated suppression of COX-2 expression using BPDE as a tool. We found that BPDE-induced COX-2 expression was through inhibition of RAR-b 2 and consequently, induction of epidermal growth factor receptor (EGFR), extracellular signal-regulated protein kinases 1/2 (Erk1/2) phosphorylation, and c-Jun expression. Esophageal cancer cells that do not express RAR-b 2 did not respond to BPDE for induction of COX-2. BPDE was also unable to induce COX-2 expression after RAR-b 2 expression was manipulated in these esophageal cancer cells. Furthermore, BPDE induced time-dependent methylation of RAR-b 2 gene promoter in esophageal cancer cells. Transfection of RAR-b 2 expression vector into esophageal cancer cells suppressed expression of EGFR, Erk1/2 phosphorylation, c-Jun, and COX-2. In addition, co-treatment of RAR-b 2 -positive cells with BPDE and the MEK1/2 inhibitor U0126 caused little change in c-Jun and COX-2 expression. This study demonstrated that BPDE-suppressed expression of RAR-b 2 results in COX-2 induction and restoration of RAR-b 2 expression reduces COX-2 protein in esophageal cancer cells, thereby further supporting our previous finding that RAR-b 2 plays an important role in suppressing esophageal carcinogenesis.

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“…The metabolized adducts may exert harmful effects. For example, the break down products of beta-carotene have been noted to interfere with retinoid signaling [189]. Further, the risk of toxicity was found to be greater among smokers who were also drinkers.…”

Section: Mechanism Of Adverse Actionsmentioning

confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

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The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

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Retinoid Signaling and Activator Protein-1 Expression in Ferrets Given -Carotene Supplements and Exposed to Tobacco Smoke

Abstract: Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.

Cited by 330 publications

References 33 publications

Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors

Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

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