γ-l-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-
benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-l-
cysteinylglycine sodium salt (
ESeroS-GS) is a water-soluble derivative of α-
tocopherol (
vitamin E). We reported previously that
ESeroS-GS can act as an
anti-inflammatory agent and can induce cell death in
breast cancer cells. However, the potential
antioxidant capacities of
ESeroS-GS remain elusive. Here, we measured its scavenging effects on
free radicals and evaluated its protective effects on neuronal cells against oxidative stress. The results indicated that
ESeroS-GS effectively scavenged both 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonate
free radicals (
ABTS(•+)) and
2,2-diphenyl-1-picrylhydrazyl (DPPH)
free radicals, and attenuated H₂O₂-induced neuronal cell death. H₂O₂ treatment induced lysosomal membrane permeabilization rapidly, and caused the redistribution of lysosomal
proteases, which were responsible for the neuronal cell death.
ESeroS-GS abolished the interaction between tBid and the lysosomal membranes, blocked the translocation of tBid to the lysosomal membranes, decreased its oligomerization within the membrane circumstances, prevented the lysosomal membrane permeabilization, and thus attenuated the neuronal cell death. These data suggest that
ESeroS-GS protected the neuronal cells from oxidative stress by stabilizing lysosomal membranes, and thus might act as a novel neuroprotector for neuronal diseases associated with oxidative stress.