Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, and Institute of Oral Science, Gangneung, Korea.
Department of Oral Pathology, College of Dentistry, Gangneung-Wonju National University, and Institute of Oral Science, Gangneung, Korea.
Sci Rep. 2019 Mar 4;9(1):3379. doi: 10.1038/s41598-019-38946-4.
4-Hexylresorcinol (4HR) is a small organic compound that is used as an additive antiseptic and antioxidant, but its molecular properties have not been clearly elucidated. The present study explored the cellular effects of 4HR on RAW 264.7 cells by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 216 antisera. 4HR-treated cells showed significant decreases in the expressions of proliferation-related proteins, cMyc/MAX/MAD network, p53/Rb/E2F and Wnt/β-catenin signalings, epigenetic modifications, and protein translation. Furthermore, 4HR suppressed the expressions of growth factors and proteins associated with RAS signaling, NFkB signaling, inflammation, and osteogenesis, but elevated the expressions of proteins associated with p53-mediated and FAS-mediated apoptosis, T-cell immunity, angiogenesis, antioxidant, and oncogenic signaling. In a 4HR adherence assay, TNFα, PKC, osteopontin, and GADD45 were strongly adherent to 4HR-coated beads, whereas IL-6, c-caspase 3, CDK4, and c-caspase 9 were not. Many 4HR adherent proteins were expressed at lower levels in 4HR treated RAW 264.7 cells than in non-treated controls, whereas 4HR non-adherent proteins were expressed at higher levels. These observations suggest 4HR affects the expressions of proteins in an adhesion-dependent manner and that its effects on proteins are characteristic and global in RAW 264.7 cells.
4-己基间苯二酚(4HR)是一种小分子有机化合物,用作添加剂防腐剂和抗氧化剂,但它的分子性质尚未明确阐明。本研究通过使用 216 种抗血清的免疫沉淀高效液相色谱(IP-HPLC),探讨了 4HR 对 RAW 264.7 细胞的细胞效应。4HR 处理的细胞表现出与增殖相关的蛋白、cMyc/MAX/MAD 网络、p53/Rb/E2F 和 Wnt/β-catenin 信号转导、表观遗传修饰和蛋白质翻译的表达显著降低。此外,4HR 抑制了与 RAS 信号、NFkB 信号、炎症和成骨相关的生长因子和蛋白的表达,但上调了与 p53 介导和 FAS 介导的细胞凋亡、T 细胞免疫、血管生成、抗氧化和致癌信号相关的蛋白的表达。在 4HR 粘附实验中,TNFα、PKC、骨桥蛋白和 GADD45 强烈地粘附于 4HR 包被的珠上,而 IL-6、c-caspase 3、CDK4 和 c-caspase 9 则不粘附。在 4HR 处理的 RAW 264.7 细胞中,许多 4HR 粘附蛋白的表达水平低于未经处理的对照组,而 4HR 非粘附蛋白的表达水平则升高。这些观察结果表明 4HR 以依赖于粘附的方式影响蛋白的表达,并且其对蛋白的影响在 RAW 264.7 细胞中是特征性和全局性的。