Boucher JG, Ahmed S, Atlas E
Endocrinology 2016 Apr;157(4):1397-407
PMID: 27003841
Abstract
Human exposure to bisphenol A has been associated with negative health outcomes in humans and its use is now regulated in a number of countries. Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A; however, its effects on cellular metabolism and potential role as an endocrine disruptor have not been fully characterized. In the current study, we evaluated the effect of BPS on adipogenesis in primary human preadipocytes. The effect of BPS on the differentiation of human preadipocytes was determined after treatment with BPS at concentrations ranging from 0.1nM to 25μM by quantifying lipid accumulation and mRNA and protein levels of key adipogenic markers. Treatment of preadipocytes with 25μM BPS induced lipid accumulation and increased the mRNA and protein levels of several adipogenic markers including lipoprotein lipase and adipocyte protein 2 (aP2). Cotreatment of cells with the estrogen receptor antagonist ICI-182,780 significantly inhibited BPS-induced lipid accumulation and affected aP2 but not lipoprotein lipase protein levels. Cotreatment of cells with the glucocorticoid receptor antagonist RU486 had no effect on BPS-induced lipid accumulation or protein levels. Furthermore, reporter gene assays using a synthetic promoter containing peroxisome proliferator-activated receptor-γ (PPARG)-response elements and a PPARG-responsive human aP2 promoter region showed that BPS was able to activate PPARG. To our knowledge, this study is the first to show that BPS induces lipid accumulation and differentiation of primary human preadipocytes, and this effect may be mediated through a PPARG pathway.
Bisphenol Sも脂肪生成を誘発する。Dexamethasoneが脂肪生成を誘発させるPositive controlとして使われている。
レポーター遺伝子アッセイはホルモンなどの生理活性物質の働きを標的遺伝子の活性化を指標として検出する
方法。
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レポーター遺伝子とは、ある遺伝子が発現しているかどうかを容易に判別するために、その遺伝子に組換える別の遺伝子のこと。緑色蛍光タンパク質(GFP)が有名。
組換えDNA技術によって作成された組換え遺伝子が、いつどこでどのくらいできているのかを比較的簡単に確認できるようにレポーター遺伝子が使用される。
通常、レポーター遺伝子自体には可視化する以外の機能は想定されていないことになっている。様々な生物の遺伝子がプロモーターの活性や蛋白質の挙動を知るためのレポーター遺伝子として利用されている。(Wikipedia)