Protective Effect of Fucoidan against MPP+-Induced SH-SY5Y Cells Apoptosis by Affecting the PI3K/Akt Pathway.

The main pathologic changes of the Parkinson's disease (PD) is dopaminergic (DA) neurons lost. Apoptosis was one of the important reasons involved in the DA lost. Our previous study found a fucoidan fraction sulfated heterosaccharide (UF) had neuroprotective activity. The aim of this study was to clarify the mechanism of UF on DA neurons using human dopaminergic neuroblastoma (SH-SY5Y) cells a typical as a PD cellular model. Results showed that UF prevented MPP+-induced SH-SY5Y cells apoptosis and cell death. Additionally, UF pretreated cells increased phosphorylation of Akt, PI3K and NGF, which means UF-treated active PI3K-Akt pathway. Moreover, UF treated cells decreased the expression of apoptosis-associated protein, such as the ratio of Bax/Bcl-2, GSK3ß, caspase-3 and p53 nuclear induced by MPP+. This effect was partially blocked by PI3K inhibitor LY294002. Our data suggested that protective effect of UF against MPP+-induced SH-SY5Y cells death by affecting the PI3K-Akt pathway. These findings contribute to a better understanding of the critical roles of UF in treating PD and may elucidate the molecular mechanisms of UF effects in PD.

The effect of different substitute groups and molecular weights of fucoidan on neuroprotective and anticomplement activity.

Ten fucoidan (FPS) derivatives were successfully synthesized, and their potential neuroprotective and anticomplement activities were investigated employing various established in vitro systems. The aim of the present study was to investigate the effects of different substitute groups and molecular weights of fucoidan on neuroprotective and anticomplement activities. All FPS derivatives possessed considerable neuroprotective and anticomplement activities and had stronger activities than FPS in certain tests. The in vitro results found that sulfated and benzoylated derivatives could reverse the decreased mitochondrial activity and decreased lactate dehydrogenase (LDH) and reactive oxygen species (ROS) release induced by 6-hydroxydopamine (6-OHDA, P<0.01 or P<0.001), which provides further evidence that sulfate and benzoylate groups could enhance the neuroprotective activity of fucoidan. In anticomplement experiments, all samples showed anticomplement activity in both systems; however, the sulfated and benzoylated derivatives showed better activity than fucoidan, with higher molecular weights showing the strongest activity. Available data suggested that substituted groups of fucoidan played an important role on neuroprotective and anticomplement activities. The mechanism of the influence of the neuroprotective and anticomplement activities of samples of the substituted groups was indicated.

H. pylori α1-3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides.

Helicobacter pylori α1-3/4-fucosyltransferase (Hp3/4FT) was expressed in Escherichia coli at a level of 30 mg L-1 culture and used as a diverse catalyst in a one-pot multienzyme (OPME) system for high-yield production of l-fucose-containing carbohydrates including Lewis antigens such as Lewis a, b, and x, O-sulfated Lewis x, and sialyl Lewis x and human milk fucosides such as 3-fucosyllactose (3-FL), lacto-N-fucopentaose (LNFP) III, and lacto-N-difuco-hexaose (LNDFH) II and III. Noticeably, while difucosylation of tetrasaccharides was readily achieved using an excess amount of donor, the synthesis of LNFP III was achieved by Hp3/4FT-catalyzed selective fucosylation of the N-acetyllactosamine (LacNAc) component in lacto-N-neotetraose (LNnT).

Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3ß, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.

Structure-activity relationship of sulfated hetero/galactofucan polysaccharides on dopaminergic neuron.

Parkinson's disease (PD) is associated with progressive loss of dopaminergic neurons and more-widespread neuronal changes that cause complex symptoms. The aim of this study was to investigate the structure-activity relationship of sulfated hetero-polysaccharides (DF1) and sulfated galactofucan polysaccharides (DF2) on dopaminergic neuron in vivo and in vitro. Treatment with samples significantly ameliorated the depletion of both DA and TH-, Bcl-2- and Bax-positive neurons in MPTP-induced PD mice, DF1 showed the highest activity. The in vitro results found that DF1 and DF2 could reverse the decreased mitochondrial activity and the increased LDL release induced by MPP(+) (P<0.01 or P<0.001) which provides further evidence that DF1 and DF2 also exerts a direct protection against the neuronal injury caused by MPP(+). Furthermore, the administration of samples effectively decreased lipid peroxidation and increased the level/activities of GSH, GSH-PX, MDA and CAT in MPTP mice. Thus, the neuron protective effect may be mediated, in part, through antioxidant activity and the prevention of cell apoptosis. The chemical composition of DF1, DF2 and DF differed markedly, the DF1 fraction had the most complex chemical composition and showed the highest neuron protective activity. These results suggest that diverse monosaccharides and uronic acid might contribute to neuron protective activity.

The protective effect of fucoidan in rats with streptozotocin-induced diabetic nephropathy.

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the ß2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications.

[Phylogenetic analysis and nitrogen removal characteristics of a heterotrophic nitrifying-aerobic denitrifying bacteria strain from marine environment].

OBJECTIVE: We determined the phylogenetic position of a heterotrophic nitrifying-aerobic denitrifying bacterium X3, and detected its nitrogen removal characteristics for providing evidence to explain the principle of heterotrophic nitrification-aerobic denitrification and to improve the process in purification of marine-culture wastewater. METHODS: The evolutionary position of the strain was determined based on its morphological, physiological, biochemical characteristics and 16SrRNA gene sequence. The nitrification-denitrification ability of this strain was detected by detecting its nitrogen removal efficiency and growth on different inorganic nitrogen source. RESULTS: Strain X3 was identified as Halomonas sp. It grew optimally at salinity 3%, pH 8.5, C:N 10:1 at 28 degrees C, and it could still survive at 15% salinity. The removal of NH4+ -N, NO2(-) -N and NO3(-) -N was 98.29%, 99.07%, 96.48% respectively within 24 h. When three inorganic nitrogen existed simultaneously, it always utilized ammonia firstly, and the total inorganic nitrogen removal was higher than with only one nitrogen, suggesting that strain X3 has the ability of simultaneous nitrification and denitrification and completing the whole nitrogen removing process. CONCLUSION: Strain X3 belonged to the genus of Halomonas. It had strong simultaneous nitrification and denitrification capability and could live in high-salinity environment.