Astaxanthin Protects PC12 Cells against Homocysteine- and Glutamate-Induced Neurotoxicity

被引:17
作者
Chang, Chi-Huang [1 ]
Chen, Kuan-Chou [2 ,3 ,4 ]
Liaw, Kuo-Chun [1 ]
Peng, Chiung-Chi [4 ]
Peng, Robert Y. [1 ]
机构
[1] Hungkuang Univ, Coll Med & Hlth Care, Dept Biotechnol, 1018,Sec 6,Taiwan Blvd, Taichung 43302, Taiwan
[2] Taipei Med Univ, Coll Med, Sch Med, Dept Urol, 250 Wu Shing St, Taipei 11031, Taiwan
[3] Taipei Med Univ, Dept Urol, Shuang Ho Hosp, 291 Zhong Zheng Rd, Taipei 23561, Taiwan
[4] Taipei Med Univ, Coll Med, Grad Inst Clin Med, 250 Wu Hsing St, Taipei 11031, Taiwan
关键词
PC12; cells; glutamate (Glu); homocysteine (Hcy); intrinsic apoptotic pathways; neuroprotective; astaxanthin (ATX); CYTOCHROME-C RELEASE; INDUCED APOPTOSIS; CALCIUM INFLUX; ER STRESS; MECHANISMS; CASPASE-12; KINASE; INJURY; BRAIN; EXCITOTOXICITY;
D O I
10.3390/molecules25010214
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Memory impairment has been shown to be associated with glutamate (Glu) excitotoxicity, homocysteine (Hcy) accumulation, and oxidative stress. We hypothesize that Glu and Hcy could damage neuronal cells, while astaxanthin (ATX) could be beneficial to alleviate the adverse effects. Using PC12 cell model, we showed that Glu and Hcy provoked a huge amount of reactive oxygen species (ROS) production, causing mitochondrial damage at EC50 20 and 10 mm, respectively. The mechanisms of action include: (1) increasing calcium influx; (2) producing ROS; (3) initiating lipid peroxidation; (4) causing imbalance of the Bcl-2/Bax homeostasis; and (5) activating cascade of caspases involving caspases 12 and 3. Conclusively, the damages caused by Glu and Hcy to PC12 cells can be alleviated by the potent antioxidant ATX.
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页数:17
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