Abstract
The present study aims to explore the neuro-protective effects of purified Sparassis crispa polysaccharides against l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cell damages and its underlying mechanisms. The Sparassis crispa water extract was purified by a DEAE-52 cellulose anion exchange column and a Sepharose G-100 column. A fraction with a molecular weight of 75 kDa and a diameter of 88.9 nm, entitled SCWEA, was obtained. SCWEA was identified with a triple helix with (1→3)-linked Rha in the backbone, and (1→2) linkages and (1→6) linkages in the side bone. Our results indicated that the pre-treatment of DPC12 cells with SCWEA prior to l-Glu exposure effectively reversed the reduction on cell viability (by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay) and reduced l-Glu-induced apoptosis (by Hoechst staining). SCWEA decreased the accumulation of intracellular reactive oxygen species, blocked Ca2+ influx and prevented depolarization of the mitochondrial membrane potential in DPC12 cells. Furthermore, SCWEA normalized expression of anti-apoptotic proteins in l-Glu-explored DPC12 cells. These results suggested that SCWEA protects against l-Glu-induced neuronal apoptosis in DPC12 cells and may be a promising candidate for treatment against neurodegenerative disease.
Highlights
Neurodegenerative disorders, which include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), have received great attention due to their devastating nature and limited treatment options
As one of the pathological factors in cerebral ischemia disease, glutamate is able to induce neuronal cell apoptosis via opening mitochondrial permeability transition pores and reducing mitochondrial membrane potential (MMP), which is initiated by the interaction between pro- and anti-apoptotic B-cell lymphoma 2 (Bcl-2) family members [3]
Our data revealed that the purified polysaccharides improved cell viability and mitochondrial function, and restored the abnormal expression of apoptosis-related proteins. All these findings demonstrated that mitochondria-related pathways are essential for the neuro-protective effects of Sparassis crispa polysaccarides against L-Glu-induced toxicity in differentiated PC12 (DPC12) cells
Summary
Neurodegenerative disorders, which include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), have received great attention due to their devastating nature and limited treatment options. During the process of neurological disorders, neurons manifest common pathological features, such as mitochondrial dysfunction and protein aggregation [1]. As one of the pathological factors in cerebral ischemia disease, glutamate is able to induce neuronal cell apoptosis via opening mitochondrial permeability transition pores (mPTP) and reducing mitochondrial membrane potential (MMP), which is initiated by the interaction between pro- and anti-apoptotic B-cell lymphoma 2 (Bcl-2) family members [3]. As a primary downstream mediator of phosphatidylinositol-3 kinase (PI3K), Protein Kinase B (AKT) preserves mitochondrial integrity by regulating the Bcl-2 family [4]. The Ca2+ influx is involved in glutamate-induced cell apoptosis by mediating the opening of mPTP [6]
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