Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.
Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.
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DOI：
10.1371/journal.pone.0052354
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xu A
中科院分区：
文献类型：
--
作者：
Chan KH;Lam KS;Cheng OY;Kwan JS;Ho PW;Cheng KK;Chung SK;Ho JW;Guo VY;Xu A
β-淀粉样蛋白(A-β)神经毒性在阿尔茨海默病(AD)发病机制中起重要作用。β神经毒性可引起氧化应激、炎症和线粒体损伤，导致神经元变性和死亡。氧化应激、炎症反应和线粒体衰竭也是以胰岛素抵抗为特征的2型糖尿病的病理生理机制。有趣的是，T2 DM增加了患AD的风险，AD与神经元胰岛素敏感性降低(中枢胰岛素抵抗)有关。我们研究了脂联素(一种具有胰岛素增敏、抗炎和抗氧化特性的脂肪因子)对人神经母细胞瘤细胞(SH-SY5Y)Aβ神经毒性的潜在保护作用。该突变体转染瑞典淀粉样前体蛋白(Sw-APP)突变体，过量产生Aβ，细胞内Aβ异常积聚。通过测定细胞死亡和裂解时释放的乳酸脱氢酶(LDH)来测定细胞毒性。结果表明，与空载体转染组相比，转染组脂联素受体1和2的表达增强，腺苷活化蛋白激酶和核转录因子-κB的活性增强。重要的是，生理浓度为10微克/毫升的脂联素可保护转导SW-APP的SH-SY5Y细胞免受过氧化氢诱导的细胞毒性。脂联素在氧化应激条件下对Aβ神经毒性诱导的细胞毒性的神经保护作用包括：1)通过内体适配器蛋白APPL1(具有磷酸酪氨酸结合、Pleckstrin同源结构域和亮氨酸拉链基序的接头蛋白)介导AMPK的激活；2)抑制NF-κB的激活。这增加了AD新疗法的可能性，如脂联素受体激动剂。
Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.
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影响因子：
3.8
作者：
de la Monte SM
通讯作者：
de la Monte SM
影响因子：
5.3
作者：
Crouch, PJ;Blake, R;Trounce, IA
通讯作者：
Trounce, IA
DOI：
10.3233/jad-2010-1308
发表时间：
2010
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Greco SJ;Bryan KJ;Sarkar S;Zhu X;Smith MA;Ashford JW;Johnston JM;Tezapsidis N;Casadesus G
通讯作者：
Casadesus G
DOI：
10.1073/pnas.0610068104
发表时间：
2007-04-24
影响因子：
11.1
作者：
Dasgupta, Biplab;Milbrandt, Jeffrey
通讯作者：
Milbrandt, Jeffrey
DOI：
10.1073/pnas.90.2.567
发表时间：
1993-01-15
影响因子：
11.1
作者：
ARISPE, N;ROJAS, E;POLLARD, HB
通讯作者：
POLLARD, HB