The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by α-synuclein or amyloid-β (1-42) peptide
The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by α-synuclein or amyloid-β (1-42) peptide
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DOI：
10.1111/j.1471-4159.2009.06228.x
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发表时间：
2009-09-01
影响因子：
4.7
通讯作者：
Forloni, Gianluigi
中科院分区：
文献类型：
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作者：
Albani, Diego;Polito, Letizia;Forloni, Gianluigi
人类sirtuins是一个由7个保守蛋白（SIRT1-7）组成的家族。研究最多的是沉默交配型信息调节-2同源物（SIRT1, NM_012238），它与多聚谷氨酰胺毒性或阿尔茨海默病（AD）模型中的神经保护有关，并被植物化合物白藜芦醇（RES）激活。我们研究了RES在氧化应激细胞模型中的神经保护作用，氧化应激是神经变性的共同特征。RES可防止过氧化氢或6-羟基多巴胺（6-OHDA）引起的毒性。这种作用可能是由SIRT1激活介导的，因为当SIRT1抑制剂sirtinol存在时，当SIRT1表达被siRNA方法下调时，保护作用就会丧失。RES还能够保护SK-N-BE免受两种易聚集蛋白引起的毒性，ad相关淀粉样蛋白β(1-42)肽（A β 42）和熟悉的帕金森病相关α -突触核蛋白（A30P） [α -syn(A30P)]。添加sirtinol可以恢复α -syn（A30P）的毒性，而即使存在sirtinol也可以发现部分RES对a β 42的保护作用，这表明RES对a β 42原纤维有直接作用。我们得出结论，在我们的神经母细胞瘤模型中，RES激活SIRT1可以防止氧化应激或α -syn（A30P）聚集引发的有害影响，而RES对a β 42表现出SIRT1独立的保护作用。
Human sirtuins are a family of seven conserved proteins (SIRT1-7). The most investigated is the silent mating type information regulation-2 homolog (SIRT1, NM_012238), which was associated with neuroprotection in models of polyglutamine toxicity or Alzheimer's disease (AD) and whose activation by the phytocompound resveratrol (RES) has been described. We have examined the neuroprotective role of RES in a cellular model of oxidative stress, a common feature of neurodegeneration. RES prevented toxicity triggered by hydrogen peroxide or 6-hydroxydopamine (6-OHDA). This action was likely mediated by SIRT1 activation, as the protection was lost in the presence of the SIRT1 inhibitor sirtinol and when SIRT1 expression was down-regulated by siRNA approach. RES was also able to protect SK-N-BE from the toxicity arising from two aggregation-prone proteins, the AD-involved amyloid beta (1-42) peptide (A beta 42) and the familiar Parkinson's disease linked alpha-synuclein(A30P) [alpha-syn(A30P)]. Alpha-syn(A30P) toxicity was restored by sirtinol addition, while a partial RES protective effect against A beta 42 was found even in presence of sirtinol, thus suggesting a direct RES effect on A beta 42 fibrils. We conclude that SIRT1 activation by RES can prevent in our neuroblastoma model the deleterious effects triggered by oxidative stress or alpha-syn(A30P) aggregation, while RES displayed a SIRT1-independent protective action against A beta 42.