Antioxidant effects of dehydroepiandrosterone are related to up-regulation of thioredoxin in SH-SY5Y cells

Abstract

Neuroprotective effects of dehydroepiandrosterone (DHEA) have been shown to be associated with its antioxidant properties, but the mechanisms remain unknown. Considering that the thioredoxin (Trx) system, an important cellular redox modulation system, changes under oxidative stress and could exert protective effects, the relationship between the antioxidant effects of DHEA and the Trx system regulation was explored. Using MTT assay and morphological observation, the effects of DHEA in the model of H2O2-induced oxidative stress in SH-SY5Y cells were analyzed, then RT-PCR and Western blot assay were used to detect the alteration in mRNA and protein level of Trx. The results showed that a pre-treatment of DHEA (10-100 nM) protected cells against the toxicity induced by H2O2 in a dose-dependent manner, which could be confirmed in morphological observation by phase-contract microscope. In addition, Trx mRNA transcription was inhibited by H2O2 (300 microM), which could be reversed by the pre-administration of DHEA in various concentrations (0.1100 nM). Western blot assay confirmed that protein level of Trx could be elevated by the pre-treatment of DHEA (10100 nM) with the exposure of H2O2. Taken together, these data suggest that DHEA may be useful in treating age-related neurodegenerative diseases based on its up-regulating effects on an antioxidant and neuroprotective protein thioredoxin, a substrate in the Trx redox system.