Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland.
Department of Physiotherapy, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland.
Neurotox Res. 2021 Oct;39(5):1575-1588. doi: 10.1007/s12640-021-00399-x. Epub 2021 Aug 3.
Tris (2,3-dibromopropyl) isocyanurate (TDBP-TAZTO or TBC) is a heterocyclic hexabromated flame retardant. It is widely used during the production of many synthetic compounds. High concentrations of TDBP-TAZTO were found in river water, surface sediments, soil, earthworms, and carp tissues. Moreover, it has been shown that this compound can cross the blood-brain barrier and accumulate in the gut and brain of carp. The aryl hydrocarbon receptor (AhR) has been characterized as a multifunctional intracellular sensor and receptor. AhR is an activator of cytochrome P450 1A1 and 1A2, which metabolize various toxic compounds. The aim of the study was to explain how/whether TDBP-TAZTO increases the expression and/or activity of the CYP1A1 enzyme and the AhR and TUBB3 expression during SH-SY5Y cell differentiation. SH-SY5Y cells were differentiated for 7 and 14 days using retinoic acid. Cell viability, ethoxyresorufin-O-deethylase (EROD) activity, and mRNA expression of CYP1A1, AhR, and TUBB3 were assessed. Our experiment showed that, during the differentiation process, the ability of TDBP-TAZTO to induce EROD activity in SH-SY5Y cells subsequently decreased, which may have been an effect of cell differentiation into neurons. Moreover, the results suggest that TDBP-TAZTO can affect the differentiation process. Since no CYP2B6 mRNA expression was detected, the CAR receptor may not be involved in the TDBP-TAZTO mechanism of action. However, more research is needed in this field to elucidate this mechanism precisely.
三（2,3-二溴丙基）异氰尿酸酯（TDBP-TAZTO 或 TBC）是一种杂环六溴阻燃剂。它广泛用于许多合成化合物的生产过程中。在河水、地表沉积物、土壤、蚯蚓和鲤鱼组织中都发现了高浓度的 TDBP-TAZTO。此外，已经表明这种化合物可以穿过血脑屏障并在鲤鱼的肠道和大脑中积累。芳香烃受体（AhR）已被描述为一种多功能细胞内传感器和受体。AhR 是细胞色素 P450 1A1 和 1A2 的激活剂，可代谢各种有毒化合物。本研究的目的是解释 TDBP-TAZTO 如何/是否会增加 CYP1A1 酶和 AhR 的表达和/或活性，以及 TUBB3 在 SH-SY5Y 细胞分化过程中的表达。使用视黄酸将 SH-SY5Y 细胞分化 7 天和 14 天。评估细胞活力、乙氧基 RESORUFIN-O-去乙基酶（EROD）活性以及 CYP1A1、AhR 和 TUBB3 的 mRNA 表达。我们的实验表明，在分化过程中，TDBP-TAZTO 诱导 SH-SY5Y 细胞 EROD 活性的能力随后降低，这可能是细胞分化为神经元的影响。此外，结果表明 TDBP-TAZTO 可以影响分化过程。由于未检测到 CYP2B6 mRNA 的表达，因此 CAR 受体可能不参与 TDBP-TAZTO 的作用机制。然而，需要在这一领域进行更多的研究，以准确阐明这一机制。
