Chen Jong-Hang, Chou Chin-Cheng
Institute of Cellular and System Medicine, National Health Research Institutes, No. 35, Keyan Rd., Miaoli 350, Taiwan.
School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan.
Food Chem Toxicol. 2015 Aug;82:27-35. doi: 10.1016/j.fct.2015.04.030. Epub 2015 May 7.
This study explores human neuroblastoma (SH-SY5Y) and human glioblastoma (U-1240 MG) cellular differentiation changes under exposure to acrylamide (ACR). Differentiation of SH-SY5Y and U-1240 MG cells were induced by retinoic acid (RA) and butyric acid (BA), respectively. Morphological observations and MTT assay showed that the induced cellular differentiation and cell proliferation were inhibited by ACR in a time- and dose-dependent manner. ACR co-treatment with RA attenuated SH-SY5Y expressions of neurofilament protein-L (NF-L), microtubule-associated protein 1b (MAP1b; 1.2 to 0.7, p < 0.001), MAP2c (2.2 to 0.8, p < 0.05), and Janus kinase1 (JAK1; 1.9 to 0.6, p < 0.001), while ACR co-treatment with BA attenuated U-1240 MG expressions of glial fibrillary acidic protein (GFAP), MAP1b (1.2 to 0.6, p < 0.001), MAP2c (1.5 to 0.7, p < 0.01), and JAK1 (2.1 to 0.5, p < 0.001), respectively. ACR also decreased the phosphorylation of extracellular-signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) in U-1240 MG cells, while caffeine reversed this suppression of ERK and JNK phosphorylation caused by ACR treatment. These results showed that RA-induced neurogenesis of SH-SY5Y and BA-induced astrogliogenesis of U-1240 MG cells were attenuated by ACR and were associated with down-regulation of MAPs expression and JAK-STAT signaling.
本研究探讨了人神经母细胞瘤（SH-SY5Y）和人胶质母细胞瘤（U-1240 MG）细胞在丙烯酰胺（ACR）暴露下的分化变化。分别用视黄酸（RA）和丁酸（BA）诱导SH-SY5Y和U-1240 MG细胞分化。形态学观察和MTT分析表明，ACR以时间和剂量依赖性方式抑制诱导的细胞分化和细胞增殖。ACR与RA共同处理减弱了SH-SY5Y中神经丝蛋白-L（NF-L）、微管相关蛋白1b（MAP1b；从1.2降至0.7，p＜0.001）、MAP2c（从2.2降至0.8，p＜0.05）和Janus激酶1（JAK1；从1.9降至0.6，p＜0.001） 的表达，而ACR与BA共同处理分别减弱了U-1240 MG中胶质纤维酸性蛋白（GFAP）、MAP1b（从1.2降至0.6，p＜0.001）、MAP2c（从1.5降至0.7，p＜0.01）和JAK1（从2.1降至0.5，p＜0.001）的表达。ACR还降低了U-1240 MG细胞中细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）的磷酸化，而咖啡因逆转了ACR处理对ERK和JNK磷酸化的这种抑制作用。这些结果表明，ACR减弱了RA诱导的SH-SY5Y神经发生和BA诱导的U-1240 MG细胞星形胶质细胞生成，并且与微管相关蛋白（MAPs）表达下调和JAK-STAT信号传导有关。
