Lee Ah Young, Choi Ji Myung, Lee Myoung Hee, Lee Jaemin, Lee Sanghyun, Cho Eun Ju
Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University, Busandaehak-ro 63 beon-gil 2, Geumjeong-gu, Busan 46241, Korea.
Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Gyeongnam 50424, Korea.
Nutr Res Pract. 2018 Apr;12(2):93-100. doi: 10.4162/nrp.2018.12.2.93. Epub 2018 Mar 21.
BACKGROUND/OBJECTIVE: Oxidative stress plays a key role in neuronal cell damage, which is associated with neurodegenerative disease. The aim of present study was to investigate the neuroprotective effects of perilla oil (PO) and its active component, alpha-linolenic acid (ALA), against hydrogen peroxide (HO)-induced oxidative stress in SH-SY5Y neuronal cells.
MATERIALS/METHODS: The SH-SY5Y human neuroblastoma cells exposed to 250 µM HO for 24 h were treated with different concentrations of PO (25, 125, 250 and 500 µg/mL) and its major fatty acid, ALA (1, 2.5, 5 and 25 µ/mL). We examined the effects of PO and ALA on HO-induced cell viability, lactate dehydrogenase (LDH) release, and nuclear condensation. Moreover, we determined whether PO and ALA regulated the apoptosis-related protein expressions, such as cleaved-poly ADP ribose polymerase (PARP), cleaved caspase-9 and -3, BCL-2 and BAX.
Treatment of HO resulted in decreased cell viability, increased LDH release, and increase in the nuclei condensation as indicated by Hoechst 33342 staining. However, PO and ALA treatment significantly attenuated the neuronal cell death, indicating that PO and ALA potently blocked the HO-induced neuronal apoptosis. Furthermore, cleaved-PARP, cleaved caspase-9 and -3 activations were significantly decreased in the presence of PO and ALA, and the HO-mediated up-regulated BAX/BCL-2 ratio was blocked after treatment with PO and ALA.
PO and its main fatty acid, ALA, exerted the protective activity from neuronal oxidative stress induced by HO. They regulated apoptotic pathway in neuronal cell death by alleviation of BAX/BCL-2 ratio, and down-regulation of cleaved-PARP and cleaved caspase-9 and -3. Although further studies are required to verify the protective mechanisms of PO and ALA from neuronal damage, PO and ALA are the promising agent against oxidative stress-induced apoptotic neuronal cell death.
背景/目的：氧化应激在神经元细胞损伤中起关键作用，这与神经退行性疾病相关。本研究的目的是探讨紫苏油（PO）及其活性成分α-亚麻酸（ALA）对过氧化氢（HO）诱导的SH-SY5Y神经元细胞氧化应激的神经保护作用。
材料/方法：将暴露于250μM HO 24小时的SH-SY5Y人神经母细胞瘤细胞用不同浓度的PO（25、125、250和500μg/mL）及其主要脂肪酸ALA（1、2.5、5和25μ/mL）处理。我们检测了PO和ALA对HO诱导的细胞活力、乳酸脱氢酶（LDH）释放和核浓缩的影响。此外，我们确定PO和ALA是否调节凋亡相关蛋白的表达，如裂解的聚ADP核糖聚合酶（PARP）、裂解的半胱天冬酶-9和-3、BCL-2和BAX。
HO处理导致细胞活力降低、LDH释放增加，且经Hoechst 33342染色显示核浓缩增加。然而，PO和ALA处理显著减轻了神经元细胞死亡，表明PO和ALA有效地阻断了HO诱导的神经元凋亡。此外，在PO和ALA存在的情况下，裂解的PARP、裂解的半胱天冬酶-9和-3的激活显著降低，且PO和ALA处理后阻断了HO介导的BAX/BCL-2比值上调。
PO及其主要脂肪酸ALA对HO诱导的神经元氧化应激具有保护活性。它们通过减轻BAX/BCL-2比值以及下调裂解的PARP和裂解的半胱天冬酶-9和-3来调节神经元细胞死亡中的凋亡途径。尽管需要进一步研究来验证PO和ALA对神经元损伤的保护机制，但PO和ALA是对抗氧化应激诱导的凋亡性神经元细胞死亡的有前景的药物。
