Melatonin Prevents the Injury-Induced Decreases of Peroxiredoxin- 2 and Thioredoxin in Brain Tissue and HT22 Cells

Abstract

Peroxiredoxin-2 and thioredoxin exert neuroprotective effects against oxidative stress. Melatonin acts asan antioxidant agent and protects neuronal cells against ischemic brain damage. This study investigatedwhether melatonin regulates peroxiredoxin-2 and thioredoxin levels in middle cerebral artery occlusion(MCAO)-induced injury and glutamate exposure-induced neuronal cell death. Adult male rats weretreated with vehicle or melatonin prior to MCAO. Brains were collected at 24 hr after MCAO and thecerebral cortices were isolated. Proteomics and Western blot analyses demonstrated that ischemic injuryinduces decreases in peroxiredoxin-2 and thioredoxin proteins. Melatonin pretreatment prevented theinjury-induced decreases in peroxiredoxin-2 and thioredoxin. Glutamate exposure induced decreases inperoxiredoxin-2 and thioredoxin in hippocampal-derived cell lines, and melatonin pretreatment preventedthe glutamate toxicity-induced decreases in peroxiredoxin-2 and thioredoxin. These results suggest thatmelatonin mediates neuroprotective effects during neuronal cell damage by preventing injury-induceddecreases in peroxiredoxin-2 and thioredoxin.