A complex AhR/ERα cross-talk at the transcriptional level was demonstrated in the human hepatoma cell line HepG2 applying specifically designed transient transfection assays OSI-744 supplier with co-transfection of hERα and the supplementation of antagonists of both the ERα and AhR receptors. TCDD demonstrated an anti-estrogenic action via down-regulation of the E2-mediated induced ERα-signaling. This anti-estrogenic action is supposed to occur via an indirect activation of ERα since TCDD alone had no effect on ERα-dependent transcriptional activity. At the same time enhanced AhR activation was observed dependent on ERα resulting in enhanced XRE-driven reporter gene expression but not in enhanced expression of
the AhR target genes CYP1A1 and 1B1. Thus, concomitant selleck compound effects of TCDD and E2 resulted in anti-estrogenic activity and an enhancement of certain but not all AhR-dependent
transcriptional activities. This study provides further evidence that AhR/ERα cross-talk can play a crucial role in the regulation of estrogen-mediated and TCDD-related mechanism of action in the liver. Different responses in HepG2 cells compared to cells derived from mainly hormone-regulated tissues may indicate that the involved molecular mechanisms of the ER and AhR signaling differ in cell- or tissue-dependent manner such as receptor levels or available co-regulatory proteins that may interact with the receptors. Overall, HepG2 cell line is an appropriate tool to further elucidate the molecular mechanisms in the liver which are involved in the nuclear receptor interactions. The mechanism of estrogen receptor signaling alteration by TCDD-activated AhR is important to understand the estrogen-related adverse effects of TCDD on the liver as one of its target organs. The authors thank Dr. Hans-Joachim Schmitz at the University of Kaiserslautern for proof Cediranib (AZD2171) reading the article. “
“Monosodium glutamate (MSG), a white crystalline
powder, is the sodium salt of a naturally occurring non-essential amino acid, glutamic acid . MSG is commonly marketed as a flavor enhancer and is used as a food additive particularly in West African and Asian dishes . Generally, MSG is accepted as a safe food additive that needs no specified average daily intake or an upper limit intake . However, inadvertent abuse of this food additive may occur because of its abundance, mostly without labelling, in many food ingredients . MSG – is the sodium salt of glutamic acid (). MSG contains 78% of glutamic acid, 22% of sodium and water . Glutamate is one of the most common amino acids found in nature and is the main component of many proteins and peptides of most tissues. Glutamate is also produced in the body and plays an essential role in human metabolism. MSG is a widely used flavor enhancing food additive that may be present in packaged foods without appearing on the label. This flavor enhancer, not very long ago, was isolated in the laboratory, and identified as MSG.