title: Anti-oxidation and Antiapoptotic Effects of Chondroitin Sulfate on 6-Hydroxydopamine-Induced Injury Through the Up-Regulation of Nrf2 and Inhibition of Mitochondria-Mediated Pathway.
abstract: The purpose of the study was to investigate the protective effect and molecular mechanism of chondroitin sulfate (CS) against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that CS could protect SH-SY5Y cells against 6-OHDA-induced injury. The subsequent mechanism study showed that the anti-oxidation of CS may partly be mediated through inhibiting the intracellular reactive oxygen species overproduction, recovering the reduction of nuclear NF-E2-related factor-2 (Nrf2) expression and the reduction of antioxidants activity induced by 6-OHDA. Furthermore, CS pretreatment significantly attenuated 6-OHDA-induced cell apoptosis and nuclear condensation. 6-OHDA-induced dysfunctions, including the decrease of mitochondrial membrane potential (ΔΨm), increase of intracellular free Ca(2+), imbalance of Bcl-2/Bax ratio, release of Cyt-c from the mitochondria and activation of caspase-3 and caspase-9 were attenuated by CS pretreatment, which demonstrated that CS suppressed 6-OHDA-induced apoptosis in SH-SY5Y cells possibly through mitochondria protection. These results suggest that CS exhibits anti-oxidation through the up-regulation of Nrf2 along with endogenous antioxidant, and reduces apoptosis via inhibiting the mitochondrial pathway to protect SH-SY5Y cells damaged by 6-OHDA.
authors.affiliation: Medical College of Qingdao University, Qingdao, 266021, Shandong, China.
authors.forename: Chuanxia
authors.initials: C
authors.lastname: Ju
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Fusheng
authors.initials: F
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Dachao
authors.initials: D
authors.lastname: Wang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Lv
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D002809:Chondroitin Sulfates; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium