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Mar Drugs. 2015 Mar 12;13(3):1267-89. doi: 10.3390/md13031267.

Acetylated chitosan oligosaccharides act as antagonists against glutamate-induced PC12 cell death via Bcl-2/Bax signal pathway.

Author information

1
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. haocui2010@hotmail.com.
2
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. xialigao1214@163.com.
3
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. zhangyiran_ouc@126.com.
4
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. wwwakin@ouc.edu.cn.
5
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. glyu@ouc.edu.cn.
6
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. hsguan@ouc.edu.cn.
7
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. lijuanzhang@ouc.edu.cn.
8
Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, and Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. lchunxia@ouc.edu.cn.

Abstract

Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of β-(1→4) D-glucosamine units, have broad range of biological activities such as antitumour, antifungal, and antioxidant activities. In this study, peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan oligosaccharides (NACOs) were prepared from the COSs by chemcal modification. The structures of these monomers were identified using NMR and ESI-MS spectra. Their antagonist effects against glutamate-induced PC12 cell death were investigated. The results showed that pretreatment of PC12 cells with the PACOs markedly inhibited glutamate-induced cell death in a concentration-dependent manner. The PACOs were better glutamate antagonists compared to the COSs and the NACOs, suggesting the peracetylation is essential for the neuroprotective effects of chitosan oligosaccharides. In addition, the PACOs pretreatment significantly reduced lactate dehydrogenase release and reactive oxygen species production. It also attenuated the loss of mitochondrial membrane potential. Further studies indicated that the PACOs inhibited glutamate-induced cell death by preventing apoptosis through depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation. These results suggest that PACOs might be promising antagonists against glutamate-induced neural cell death.

PMID:
25775423
PMCID:
PMC4377983
DOI:
10.3390/md13031267
[Indexed for MEDLINE]
Free PMC Article

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