Kim Jongwan, Moon Il Soo, Goo Tae-Won, Moon Seong-Su, Seo Minchul
Institute of Medical Research, Dongguk University College of Medicine, Gyeongju 38066, Korea.
Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea.
Molecules. 2015 Nov 25;20(12):20998-1009. doi: 10.3390/molecules201219744.
Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence has suggested that Undaria pinnatifida (UP), an edible brown algae, has antioxidant activity. However, the neuroprotective effect of UP has yet to be examined. In this study, to investigate the neuroprotective effect of UP on ER stress-induced neuronal damage in mouse hypothalamic neurons, mice immortal hypothalamic neurons (GT1-7) were incubated with extract of UP. ER stress was induced by treating with tunicamycin. Tunicamycin induced apoptotic cell death was compared with the vehicle treatment through excessive ER stress. However UP protected GT1-7 cells from cell death, occurring after treatment with tunicamycin by reducing ER stress. Treatment with UP resulted in reduced increment of ATF6 and CHOP, and recovered the decrease of phosphorylation of Akt/mTOR by tunicamycin and the increment of autophagy. These results show that UP protects GT1-7 cells from ER stress induced cell death through the Akt/mTOR pathway. The current study suggests that UP may have a beneficial effect on cerebral neuronal degeneration in metabolic diseases with elevated ER stress.
内质网（ER）应激增加是下丘脑神经元损伤的原因之一，也是肥胖和糖尿病等代谢紊乱的原因之一。最近的证据表明，可食用褐藻裙带菜（UP）具有抗氧化活性。然而，UP的神经保护作用尚未得到研究。在本研究中，为了探讨UP对小鼠下丘脑神经元内质网应激诱导的神经元损伤的神经保护作用，将小鼠永生下丘脑神经元（GT1-7）与UP提取物一起孵育。用衣霉素处理诱导内质网应激。通过过度内质网应激，将衣霉素诱导的凋亡细胞死亡与载体处理进行比较。然而，UP通过降低内质网应激，保护GT1-7细胞免受衣霉素处理后发生的细胞死亡。UP处理导致ATF6和CHOP的增加减少，并恢复了衣霉素引起的Akt/mTOR磷酸化降低和自噬增加。这些结果表明，UP通过Akt/mTOR途径保护GT1-7细胞免受内质网应激诱导的细胞死亡。目前的研究表明，UP可能对内质网应激升高的代谢性疾病中的脑神经元变性具有有益作用。
