Study on the relationships between molecular weights of chondroitin sulfate oligosaccharides and Aβ-induced oxidative stress and the related mechanisms

Author:

Zhao Na1,Meng Jie2,Jiang Wenjie1,Xu Wenjia1,Liu Chunhui1,Wang Fengshan13

Affiliation:

1. Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan 250012, China

2. School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan 250012, China

3. Laboratory of Carbohydrate Chemistry and Glycobiology, National Glycoengineering Research Center, Shandong University, No. 44 West Wenhua Road, Jinan 250012, China

Abstract

Abstract In the present study, we studied anti-Alzheimer′s disease (AD) activities of chondroitin sulfate (CS) oligosaccharides with different molecular weights. CS from shark cartilage was degraded by a recombinant CS endolyase, chondroitinase ABC I (CHSase ABC I), and CS disaccharide (DP2), tetrasaccharide (DP4), hexasaccharide (DP6), octasaccharide (DP8), decasaccharide (DP10) and dodecasaccharide (DP12) were obtained by separation with gel filtration. Anti-AD activities of CS oligosaccharides were assessed using Aβ-injured SH-SY5Y cells and BV2 cells. It was shown that CS oligosaccharides could block Aβ-induced oxidative stress, mitochondrial dysfunction and activation of intrinsic apoptotic pathway for SH-SY5Y cells. Furthermore, these activities increased with the increase of molecular weights. For Aβ-injured BV2 cells, CS oligosaccharides inhibited oxidative stress, the production of proinflammatory cytokines and the activation of toll-like receptor pathway, and CS DP2 had the best activity among them. In conclusion, CS oligosaccharides suppressed Aβ-induced oxidative stress and relevant injury in vitro, and these effects had different relationships with the molecular weights of CS oligosaccharides for different cell lines, which might be caused by different mechanisms.

Funder

National Natural Science Foundation of China

China–Australia Centre for Health Sciences Research

Publisher

Oxford University Press (OUP)

Subject

Biochemistry

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