Am80 induces neuronal differentiation in a human neuroblastoma NH-12 cell line.
Am80 induces neuronal differentiation in a human neuroblastoma NH-12 cell line.
复制标题
Am80 诱导人神经母细胞瘤 NH-12 细胞系的神经元分化。
DOI：
10.3892/ijmm_00000478
复制
发表时间：
2010
影响因子：
5.4
通讯作者：
M. Nakashima
中科院分区：
文献类型：
--
作者：
Hideo Shiohira;A. Kitaoka;H. Shirasawa;M. Enjoji;M. Nakashima
维甲酸类化合物包括天然维生素A及其衍生物和合成的化合物，通过维甲酸受体(RAR，RXR)作为转录因子发挥作用。全反式维甲酸(ATRA)是维甲酸家族的一员，是RAR的内源性配体，被认为是治疗急性早幼粒细胞白血病(APL)的有效分化诱导剂。全反式维甲酸疗法现在被确定为APL的初始治疗方法。最近，为了提高ATRA的疗效和减少不良反应，一种新的合成的RARα和β受体选择性激动剂Am80被开发出来并应用于APL的治疗。在这项研究中，我们测试了Am80是否能够诱导人神经母细胞瘤细胞系NH-12分化，并比较了Am80和ATRA的分化效果。形态学研究表明，AM80比全反式维甲酸诱导更强的神经突起生长，细胞毒性也更小。AM80上调原肌球蛋白相关激酶B和ATRA的表达。此外，AM80增加了神经元标记物生长相关蛋白43的表达。这些发现表明，AM80比全反式维甲酸更能诱导神经元分化，因此可能有助于建立治疗帕金森氏症等神经元退行性疾病的策略。
Retinoids including natural vitamin A, its derivatives and synthetic compounds work as transcription factors through the retinoic acid receptors (RAR, RXR). All-trans retinoic acid (ATRA), a family of retinoids, is an internal ligand of RAR and well known as a useful differentiation inducer to treat acute promyelocytic leukemia (APL). ATRA therapy is now established as an initial treatment for APL. Recently, to improve therapeutic potency and reduce adverse effects of ATRA, a novel synthetic selective agonist for RARalpha and beta, Am80, was developed and applied to APL treatment. In this study, we tested whether Am80 was capable of inducing neuronal differentiation in a human neuroblastoma cell line, NH-12 and compared the differentiation effects between Am80 and ATRA. Morphological studies demonstrated that Am80 induced more potent neurite outgrowth and also proved lesser cell toxicity than ATRA. Am80 up-regulated the expression of tropomyosin-related kinase B as well as ATRA. Moreover, Am80 increased the expression of the neuronal marker, growth-associated protein 43. These findings suggest that Am80 induces neuronal differentiation to a greater extent than ATRA and thus may help establishing therapeutic strategies against neuronal degenerative disorders such as Parkinson's disease.
DNA 微阵列分析揭示了全反式视黄酸和 Am80 诱导的 HL-60 细胞分化过程中 PI3 激酶/Akt 途径的差异调节。
DOI：
--
发表时间：
2004
期刊：
Biochemical Pharmacology 68
影响因子：
--
作者：
S.Ishida;Y.Shigemoto-Mogami;Y.Shinozaki;H.Kagechika;K.Shudo;S.Ozawa;J.Sawada;Y.Oh
通讯作者：
Y.Oh