Acetylated Chitosan Oligosaccharides Act as Antagonists against Glutamate-Induced PC12 Cell Death via Bcl-2/Bax Signal Pathway

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.

Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with β-Amyloid Aggregation and Alleviate β-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner

“…Wu et al reported that COS and their derivatives may be able to inhibit apoptosis of neuronal cells in brain cells [ 39 ]. Hao et al discovered that PC12 cells pretreated with per-acetylated chitosan oligosaccharides significantly inhibited glutamate-induced cell apoptosis through regulating elevation of the Bax/Bcl-2 ratio and activation of caspase-3 [ 40 ]. Moreover, water-soluble chitosan with high molecular weights could protect against cell apoptosis induced by serum starvation in human astrocytes [ 41 ].…”

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

“…On the other hand, there was no significant change in the gene expression of Bcl‐2 (anti‐apoptosis gene). Hao et al also reported that Bax was significantly inhibited, but there was no change in Bcl‐2 expression after chitosan oligosaccharide treatment in a glutamate‐induced cell death model in a PC12 cell line . Therefore, it is possible that cells related to the allergic response undergo apoptosis more frequently due to upregulation of pro‐apoptotic gene.…”

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell

“…Bcl-2/Bax jointly acts on the outer membrane of the mitochondria, and the ratio between these affects the apoptosis or survival of cells. 10 The overexpression of Bax can antagonize the protective effect of Bcl-2, and induce cell death. The overexpression of Bcl-xL can be found in many tumors; hence, the inhibition of the overexpression of Bcl-2 and Bcl-xL and other antiapoptotic proteins, as well as the recovery of their apoptosis pathway signals and protein expression, are strategies and directions of tumor treatment that are currently to some extent.…”