title: Neuroprotective effect of sulfated polysaccharide isolated from sea cucumber Stichopus japonicus on 6-OHDA-induced death in SH-SY5Y through inhibition of MAPK and NF-κB and activation of PI3K/Akt signaling pathways.
abstract: The purpose of this study is to investigate the protective effect and molecular mechanism of the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus against 6-OHDA-induced toxicity in SH-SY5Y cells. The results showed that SJP could protect SH-SY5Y cells against 6-OHDA-induced cell injury. We found that SJP effectively improves cell viability, decreases LDH leakage, and reverses morphological damage. Moreover, SJP significantly increases SOD activity but decreases MDA levels and ROS generation. Effect of SJP on 6-OHDA-induced cell death in SH-SY5Y cells is associated with an arrest in the G1/S phase of the cell cycle and inhibits the expression of Cyclin D3. 6-OHDA-induced intracellular generation of ROS and mitochondrial dysfunctions, release of cytochrome c, imbalance of Bax/Bcl-2, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 ratio, and p-p53 activation were strikingly attenuated by SJP pretreatment. Meanwhile, SJP counteracted NF-κB activation, thereby preventing up-regulation of iNOS and intracellular NO release. The data provide the first evidence that SJP protects SH-SY5Y cells against 6-OHDA toxicity possibly by inhibiting MAPK and NF-κB and activating PI3K/Akt signaling pathways. Thus, SJP is a candidate for further evaluation of its protective effects against neurodegeneration in PD.
authors.affiliation: Marine College, Shandong University, Weihai, Shandong, China; School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cui
authors.affiliation: Marine College, Shandong University, Weihai, Shandong, China.
authors.forename: Ningshan
authors.initials: N
authors.lastname: Cui
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Marine College, Shandong University, Weihai, Shandong, China.
authors.forename: Shuliang
authors.initials: S
authors.lastname: Song
authors.affiliation: Marine College, Shandong University, Weihai, Shandong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.affiliation: Marine College, Shandong University, Weihai, Shandong, China; School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China. Electronic address: jiaiguo@sdu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D016627:Oxidopamine / Q000008:administration & dosage; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011134:Polysaccharides / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012616:Sea Cucumbers / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013431:Sulfates / Q000008:administration & dosage
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D011134:Polysaccharides; D013431:Sulfates; D016627:Oxidopamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: 6-OHDA; MAPK; NF-κB; PD; PI3K/Akt; SH-SY5Y