Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
Biol Pharm Bull. 2012;35(9):1447-53. doi: 10.1248/bpb.b110706.
Diabetic retinopathy is a common complication of diabetes mellitus (DM). The oxidative damage inflicted on retinal pigment epithelial (RPE) cells by high glucose closely approximates the molecular basis for the loss of vision associated with this disease. We investigate a novel algae-derived polysaccharide compound for its role in protecting ARPE-19 cells from high glucose-induced oxidative damage. ARPE-19 cells were cultured for 4 d with normal concentration of D-glucose, and exposed to either normal or high concentrations of D-glucose in the presence or absence of the polysaccharide compound at variety of concentrations for another 48 h. Taurine was used as a positive control. Activity of super oxide dismutase (SOD) and concentration of glutathione (GSH) were measured as well as cytotoxicity of high glucose and the polysaccharide compound. To analyse cellular damage by high glucose, activation of Annexin V and p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) were examined. Our results showed that a significant cellular damage on ARPE-19 cells after 48 h treatment with high glucose, accompanied by a decrease in SOD activity and GSH concentration; high glucose also caused ARPE-19 cell apoptosis and activation of p38MAPK and ERK. As the non-toxic polysaccharide compound protected ARPE-19 cells from high glucose-induced cellular damage, the compound recovered SOD activity and concentration of GSH in the cells. The compound also abrogated the cell apoptosis and activation of p38MAPK and ERK. Therefore, the polysaccharide compound derived from algae extracts could be unique candidate for a new class of anti-DM and anti-oxidative damage.
糖尿病视网膜病变是糖尿病(DM)的常见并发症。高血糖对视网膜色素上皮(RPE)细胞造成的氧化损伤与该疾病相关的视力丧失的分子基础非常接近。我们研究了一种新型藻类衍生多糖化合物,以研究其在保护 ARPE-19 细胞免受高葡萄糖诱导的氧化损伤中的作用。将 ARPE-19 细胞在正常浓度的 D-葡萄糖中培养 4 天,然后在存在或不存在多糖化合物的情况下,将其暴露于正常或高浓度的 D-葡萄糖中 48 小时。牛磺酸被用作阳性对照。测量超氧化物歧化酶(SOD)的活性和谷胱甘肽(GSH)的浓度以及高葡萄糖和多糖化合物的细胞毒性。为了分析高葡萄糖引起的细胞损伤,检查 Annexin V 和 p38 丝裂原活化蛋白激酶(MAPK)和细胞外信号调节激酶(ERK)的激活。我们的结果表明,在高葡萄糖处理 48 小时后,ARPE-19 细胞会受到明显的细胞损伤,同时 SOD 活性和 GSH 浓度降低;高葡萄糖还会导致 ARPE-19 细胞凋亡并激活 p38MAPK 和 ERK。由于无毒的多糖化合物可保护 ARPE-19 细胞免受高葡萄糖诱导的细胞损伤,因此该化合物可恢复细胞中的 SOD 活性和 GSH 浓度。该化合物还可消除细胞凋亡和 p38MAPK 和 ERK 的激活。因此,从藻类提取物中获得的多糖化合物可能是新型抗糖尿病和抗氧化损伤药物的独特候选物。