Cui Chao, Cui Ningshan, Wang Peng, Song Shuliang, Liang Hao, Ji Aiguo
Marine College, Shandong University, Weihai, Shandong, China.
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
Cell Mol Neurobiol. 2015 Nov;35(8):1081-92. doi: 10.1007/s10571-015-0202-x. Epub 2015 May 8.
In this report, the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus can protect PC12 from Na2S2O4-induced hypoxia/reoxygenation (H/R) injury. SJP effectively improves cell viability and reduces extracellular LDH release in PC12 cells after H/R. Moreover, SJP significantly increases SOD activity but decreases MDA levels. Our experiments showed that SJP could significantly reduce cell apoptosis caused by H/R. Our current results demonstrate that SJP suppressed the activation of MAPKs, resulting in a significant decrease in Bax/Bcl-2 ratio, cleaved caspase-3/caspase-3, p53 phosphorylation, and cytochrome c release in a concentration-dependent manner. MAPK is closely related to H/R injury. SJP inhibited JNK1/2 and p38 MAPK activation but did not affect the increased ERK1/2 expression. These results suggested that JNK1/2 and p38 MAPK pathways could be involved in SJP-mediated attenuation of PC12 H/R injury. SJP prevented PC12 H/R injury in a dose-dependent manner, indicating that SJP may be developed as a candidate drug to prevent or treat cerebral ischemia-reperfusion injury.
在本报告中,从日本刺参中分离出的硫酸化多糖(SJP)可保护PC12细胞免受连二亚硫酸钠诱导的缺氧/复氧(H/R)损伤。H/R后,SJP可有效提高PC12细胞的活力并减少细胞外乳酸脱氢酶的释放。此外,SJP可显著提高超氧化物歧化酶(SOD)活性,但降低丙二醛(MDA)水平。我们的实验表明,SJP可显著减少H/R引起的细胞凋亡。我们目前的结果表明,SJP可抑制丝裂原活化蛋白激酶(MAPKs)的激活,导致Bax/Bcl-2比值、裂解的半胱天冬酶-3/半胱天冬酶-3、p53磷酸化以及细胞色素c释放呈浓度依赖性显著降低。MAPK与H/R损伤密切相关。SJP可抑制JNK1/2和p38 MAPK的激活,但不影响ERK1/2表达的增加。这些结果表明,JNK1/2和p38 MAPK信号通路可能参与了SJP介导的PC12细胞H/R损伤的减轻过程。SJP以剂量依赖性方式预防PC12细胞的H/R损伤,表明SJP可能被开发成为预防或治疗脑缺血再灌注损伤的候选药物。