Lim Seiyoung, Hwang Sinwoo, Yu Ji Hoon, Lim Joo Weon, Kim Hyeyoung
Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Republic of Korea.
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.
Mol Nutr Food Res. 2017 May;61(5). doi: 10.1002/mnfr.201600530. Epub 2017 Feb 6.
Regulator of calcineurin 1 (RCAN1) is located on the Down syndrome critical region (DSCR) locus in human chromosome 21. Oxidative stress and overexpression of RCAN1 are implicated in neuronal impairment in Down's syndrome (DS) and Alzheimer's disease (AD). Serum level of lycopene, an antioxidant pigment, is low in DS and AD patients, which may be related to neuronal damage. The present study is to investigate whether lycopene inhibits apoptosis by reducing ROS levels, NF-κB activation, expression of the apoptosis regulator Nucling, cell viability, and indices of apoptosis (cytochrome c release, caspase-3 activation) in RCAN1-overexpressing neuronal cells.
Cells transfected with either pcDNA or RCAN1 were treated with or without lycopene. Lycopene decreased intracellular and mitochondrial ROS levels, NF-κB activity, and Nucling expression while it reversed decrease in mitochondrial membrane potential, mitochondrial respiration, and glycolytic function in RCAN1-overexpressing cells. Lycopene inhibited cell death, DNA fragmentation, caspase-3 activation, and cytochrome c release in RCAN1-overexpressing cells.
Lycopene inhibits RCAN1-mediated apoptosis by reducing ROS levels and by inhibiting NF-κB activation, Nucling induction, and the increase in apoptotic indices in neuronal cells. Consumption of lycopene-rich foods may prevent oxidative stress-associated neuronal damage in some pathologic conditions such as DS or AD.
钙调神经磷酸酶调节因子1（RCAN1）位于人类21号染色体的唐氏综合征关键区域（DSCR）位点。氧化应激和RCAN1的过表达与唐氏综合征（DS）和阿尔茨海默病（AD）中的神经元损伤有关。抗氧化色素番茄红素的血清水平在DS和AD患者中较低，这可能与神经元损伤有关。本研究旨在探讨番茄红素是否通过降低过表达RCAN1的神经元细胞中的活性氧水平、核因子κB（NF-κB）激活、凋亡调节因子Nucling的表达、细胞活力以及凋亡指标（细胞色素c释放、半胱天冬酶-3激活）来抑制细胞凋亡。
用pcDNA或RCAN1转染的细胞分别用或不用番茄红素处理。番茄红素降低了细胞内和线粒体的活性氧水平、NF-κB活性以及Nucling的表达，同时逆转了过表达RCAN1细胞中线粒体膜电位、线粒体呼吸和糖酵解功能的降低。番茄红素抑制了过表达RCAN1细胞的细胞死亡、DNA片段化、半胱天冬酶-3激活和细胞色素c释放。
番茄红素通过降低活性氧水平以及抑制NF-κB激活、Nucling诱导和神经元细胞凋亡指标的增加来抑制RCAN1介导的细胞凋亡。食用富含番茄红素的食物可能预防某些病理状况（如DS或AD）中与氧化应激相关的神经元损伤。
