Astaxanthine Secured Apoptotic Death of PC12 Cells Induced by β-Amyloid Peptide 25-35: Its Molecular Action Targets
Astaxanthine Secured Apoptotic Death of PC12 Cells Induced by β-Amyloid Peptide 25-35: Its Molecular Action Targets
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DOI：
10.1089/jmf.2009.1291
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发表时间：
2010-06-01
影响因子：
2.4
通讯作者：
Peng, Chiung-Huei
中科院分区：
文献类型：
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作者：
Chang, Chi-Huang;Chen, Chung-Yin;Peng, Chiung-Huei
虾青素（ASTx）是一种存在于许多甲壳类动物和红酵母中的新型类胡萝卜素营养品。它具有强大的抗氧化、光保护、肝毒和抗炎活性。ASTx治疗神经退行性疾病的文献效果仍然缺乏。我们采用β -淀粉样肽（A β） 25-35处理的PC12模型来研究ASTx对神经元的保护作用。检测的参数包括细胞活力、半胱天冬酶激活和各种凋亡生物标志物，这些生物标志物在转导途径中独立或协同发挥关键作用。结果表明，A β 25-35在30 μ M剂量下可抑制细胞活力55%，而在5.00 μ M剂量下，ASTx完全无毒。0.1 μ M剂量下，ASTx可通过以下几种方式保护PC12细胞免受A β 25-35的破坏作用：(1)保护细胞活力；(2)部分下调caspase 3的激活；(3)抑制Bax的表达；(4)完全消除白细胞介素-1 β和肿瘤坏死因子-a的升高；(5)通过抑制核因子kappa B的核易位；(6)通过完全抑制p38丝裂原活化蛋白激酶的磷酸化；(7)通过彻底消除钙离子内流，有效维持钙稳态；(8)通过抑制大部分（约75%）活性氧的产生。总之，ASTx可能具有作为一种非常潜在的神经元保护剂和抗早期阿尔茨海默病辅助治疗的优点。
Astaxanthine (ASTx) is a novel carotenoid nutraceutical occurring in many crustaceans and red yeasts. It has potent antioxidant, photoprotective, hepatodetoxicant, and anti-inflammatory activities. Documented effect of ASTx on treatment of neurodegenerative disease is still lacking. We used the beta-amyloid peptide (A beta) 25-35-treated PC12 model to investigate the neuron-protective effect of ASTx. The parameters examined included cell viability, caspase activation, and various apoptotic biomarkers that play their critical roles in the transduction pathways independently or synergistically. Results indicated that A beta 25-35 at 30 mu M suppressed cell viability by 55%, whereas ASTx was totally nontoxic below a dose of 5.00 mu M. ASTx at 0.1 mu M protected PC12 cells from damaging effects of A beta 25-35 in several ways: (1) by securing the cell viability; (2) by partially down-regulating the activation of caspase 3; (3) by inhibiting the expression of Bax; (4) by completely eliminating the elevation of interleukin-1 beta and tumor necrosis factor-a; (5) by inhibiting the nuclear translocation of nuclear factor kappa B; (6) by completely suppressing the phosphorylation of p38 mitogen-activated protein kinase; (7) by completely abolishing the calcium ion influx to effectively maintain calcium homeostasis; and (8) by suppressing the majority (about 75%) of reactive oxygen species production. Conclusively, ASTx may have merit to be used as a very potential neuron protectant and an anti-early-stage Alzheimer's disease adjuvant therapy.