Shiohira Hideo, Kitaoka Akira, Enjoji Munechika, Uno Tsukasa, Nakashima Manabu
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Biomed Res. 2012;33(5):291-7. doi: 10.2220/biomedres.33.291.
Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.
合成类视黄醇Am80已用于急性早幼粒细胞白血病（APL）的分化治疗。全反式维甲酸（ATRA）作为天然类视黄醇之一，也已用于治疗APL。ATRA治疗通过诱导原肌球蛋白相关激酶B（TrkB）表达并增加对脑源性神经营养因子（BDNF，一种TrkB配体）的敏感性来引起神经元分化。在本研究中，我们研究了Am80对人神经母细胞瘤SH-SY5Y细胞中神经元分化、BDNF敏感性和TrkB表达的影响。用Am80处理可诱导神经突生长的形态学分化，并增加神经元分化标志物GAP43 mRNA的表达。此外，TrkB蛋白也增加，并且用Am80处理后外源性BDNF刺激比未进行BDNF处理诱导出更大的神经突生长。这些结果表明，Am80通过增加TrkB表达和BDNF敏感性诱导神经元分化。
