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Cigarette Smoke Extract Disrupts Transcriptional Activities Mediated by Thyroid Hormones and Its Receptors
- Source :
- Biological and Pharmaceutical Bulletin. 41:383-393
- Publication Year :
- 2018
- Publisher :
- Pharmaceutical Society of Japan, 2018.
-
Abstract
- Cigarette smoke contains over 4800 compounds, including at least 200 toxicants or endocrine disruptors. Currently, effects of cigarette smoke on thyroid hormone (TH) levels remains to be clarified. Here, we demonstrate that cigarette smoke extract (CSE) possesses thyroid hormone properties and acts synergistically as a partial agonist for thyroid hormone receptors (TRs) in the presence of TH. In transient gene expression experiments, CSE stimulated transcriptional activity with TH in a dose-dependent manner. Stimulatory effects were observed with physiological TH concentrations, although CSE did not activate TRs without TH. CSE (5%) dissolved in phosphate-buffered saline (PBS) supplemented with 1 nM TH was approximately comparable to 3.2±0.1 and 2.3±0.2 nM of TRα1 and TRβ1, respectively. To illustrate probable mechanisms of the CSE agonistic activity, effects on TR mediated transcriptional functions with cofactors were investigated. With a mammalian two-hybrid assay, CSE recruited the nuclear coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC1) to the TR. Unsaturated carbonyl compounds, acrolein, crotonaldehyde, and methyl vinyl ketone, representative constituents of CSE, retained such agonistic properties and possibly contributed to stimulatory effects. The results suggest that CSE recruits a transcriptional activator and may reinforce TH binding to the TR additively, resulting in gene expression. CSE partially agonizes TH action and may disturb the function of various nuclear hormone receptor types and their cofactors to disrupt the physiological processes.
- Subjects :
- 0301 basic medicine
Thyroid Hormones
medicine.medical_specialty
Transcription, Genetic
Pharmaceutical Science
Nerve Tissue Proteins
030209 endocrinology & metabolism
03 medical and health sciences
Nuclear Receptor Coactivator 1
0302 clinical medicine
Malate Dehydrogenase
Smoke
Internal medicine
Tobacco
parasitic diseases
Gene expression
medicine
Humans
Receptor
Pharmacology
Receptors, Thyroid Hormone
Thyroid hormone receptor
Chemistry
Thyroid Hormone Receptors beta
General Medicine
Nuclear receptor coactivator 1
HEK293 Cells
030104 developmental biology
Endocrinology
Gene Expression Regulation
Endocrine disruptor
Nuclear receptor
Signal transduction
Carrier Proteins
Thyroid Hormone Receptors alpha
Hormone
Subjects
Details
- ISSN :
- 13475215 and 09186158
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Biological and Pharmaceutical Bulletin
- Accession number :
- edsair.doi.dedup.....a2814a52e6ea8b11e487792d7ff998c8