Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin ( Heph ) and ceruloplasmin ( Cp ) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph , Cp , and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.

The hydrolysate of golden cuttlefish (Sepia esculenta) was prepared by using papain, and then, it was further separated by ultrafiltration, gel filtration chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC). The peptide components of the active fraction were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then two novel peptides, SeP2 (DVEDLEAGLAK, 1159.27 Da) and SeP5 (EITSLAPSTM, 1049.22 Da), were obtained and displayed significant alleviation effects on oxidative stress in Caenorhabditis elegans. Studies indicated that S. esculenta antioxidant peptides (SePs) increase superoxide dismutase (SOD) activity but reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levelsin oxidation-damaged nematodes. Using transgenic CF1553 nematodes, the sod-3p::GFP expression in the worms treated with SePs was significantly higher than that of the control nematodes. Real-time PCR also demonstrated that the expression of stress-related genes such as sod-3 is up-regulated by SePs. Furthermore, studies showed that SePs could obviously decrease fat accumulation as well as reduce the elevated ROS and MDA levels in high-fat nematodes. Taken together, these results indicated that SePs are capable of the activation of antioxidant defense and the inhibition of free radicals and lipid peroxidation, play important roles in attenuating oxidative stress and fat accumulation in C. elegans, and might have the potential to be used in nutraceutical and functional foods.

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