RT Journal Article
SR Electronic
T1 Chondroitin Sulfate Protects SH-SY5Y Cells from Oxidative Stress by Inducing Heme Oxygenase-1 via Phosphatidylinositol 3-Kinase/Akt
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 946
OP 953
DO 10.1124/jpet.107.123505
VO 323
IS 3
A1 Noelia Cañas
A1 Teresa Valero
A1 Mercedes Villarroya
A1 Eulàlia Montell
A1 Josep Vergés
A1 Antonio G. García
A1 Manuela G. López
YR 2007
UL http://jpet.aspetjournals.org/content/323/3/946.abstract
AB We investigated the mechanism of the neuroprotective properties of chondroitin sulfate (CS), an endogenous perineuronal net glycosaminoglycan, in human neuroblastoma SH-SY5Y cells subjected to oxidative stress. Preincubation with CS for 24 h afforded concentration-dependent protection against H2O2-induced toxicity (50 μM for 24 h) measured as lactic dehydrogenase released to the incubation media; cell death was prevented at the concentrations of 600 and 1000 μM. Cell death caused by a combination of 10 μM rotenone plus 1 μM oligomycin-A (Rot/oligo) was also reduced by CS at concentrations ranging from 0.3 to 100 μM; in this toxicity model, maximum protection was achieved at 3 μM (48%). No significant protection was observed in a cell death model of Ca2+ overload (70 mM K+, for 24 h). H2O2 and Rot/oligo generated reactive oxygen species (ROS) measured as an increase in the fluorescence of dichlorofluorescein diacetate-loaded cells. CS drastically reduced ROS generation induced by both H2O2 (extracellular ROS) and Rot/oligo (intracellular ROS). CS also increased the expression of phosphorylated Akt and heme oxygenase-1 by 2-fold. The protective effects of CS were prevented by chelerythrine, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), cycloheximide, and Sn(IV)-protoporphyrin IX. Taken together, these results show that CS can protect SH-SY5Y cells under oxidative stress conditions by activating protein kinase C, which phosphorylates Akt that, via the phosphatidylinositol 3-kinase/Akt pathway, induces the synthesis of the antioxidant protein heme oxygenase-1. The American Society for Pharmacology and Experimental Therapeutics