Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China; Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Health Toxicology, Laboratory of Modern Toxicology, Shenzhen Centre for Disease Control and Prevention, Shenzhen 518055, China; College of Food Science and Technology, Hunan Agricultural University, East Renmin Road, Changsha 410128, Hunan, China.
Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China; Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Health Toxicology, Laboratory of Modern Toxicology, Shenzhen Centre for Disease Control and Prevention, Shenzhen 518055, China.
Toxicol Lett. 2014 Aug 4;228(3):241-7. doi: 10.1016/j.toxlet.2014.05.010. Epub 2014 May 21.
Chromium is a potent human mutagen and carcinogen. The capability of chromium to cause cancers has been known for more than a century, and numerous epidemiological studies have been performed to determine its carcinogenicity. In the post-genome era, cancer has been found to relate to epigenetic mutations. However, very few researches have focused on hexavalent chromium (Cr(VI))-induced epigenetic alterations. The present study was designed to investigate whether Cr(VI) would affect the level of a newfound epigenetic modification: histone biotinylation. Histone acetylation and histone biotinylation were studied in detail using human bronchial epithelial (16HBE) cells as an in vitro model after Cr(VI) treatment. Our study showed that Cr(VI) treatment decreased histone acetylation level in 16HBE cells. In addition, low doses of Cr(VI) (≤0.6μM) elevated the level of histone biotinylation. Furthermore, immunoblot analysis of biotinidase (BTD), a major protein which maintains homeostasis of histone biotinylation, showed that the distribution of BTD became less even and more concentrated at the nuclear periphery in cells exposed to Cr(VI). Moreover, Cr(VI)-induced histone deacetylation may take part in the regulation of histone biotinylation. Together, our study provides new insight into the mechanisms of Cr(VI)-induced epigenetic regulation that may contribute to the chemoprevention of Cr(VI)-induced cancers and may have important implications for epigenetic therapy.
铬是一种有效的人类诱变剂和致癌物质。一个多世纪以来，人们已经知道铬有致癌能力，并且已经进行了许多流行病学研究来确定其致癌性。在后基因组时代，癌症已被发现与表观遗传突变有关。然而，很少有研究关注六价铬（Cr(VI)）诱导的表观遗传改变。本研究旨在探讨 Cr(VI)是否会影响一种新发现的表观遗传修饰：组蛋白生物素化。在 Cr(VI)处理后，我们使用人支气管上皮细胞（16HBE）作为体外模型，详细研究了组蛋白乙酰化和组蛋白生物素化。我们的研究表明，Cr(VI)处理降低了 16HBE 细胞中的组蛋白乙酰化水平。此外，低剂量的 Cr(VI)（≤0.6μM）会提高组蛋白生物素化水平。此外，生物素酶（BTD）的免疫印迹分析显示，生物素酶是维持组蛋白生物素化平衡的主要蛋白质，暴露于 Cr(VI)的细胞中 BTD 的分布变得不均匀，并且更集中在核周。此外，Cr(VI)诱导的组蛋白去乙酰化可能参与了组蛋白生物素化的调节。总之，我们的研究为 Cr(VI)诱导的表观遗传调控机制提供了新的见解，这可能有助于预防 Cr(VI)诱导的癌症的化学预防，并且可能对表观遗传治疗具有重要意义。
