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ISSN
1672-9145
Acta Biochim Biophys Sin
2005, 37(2): 119–125
CN 31-1940/Q
Antioxidant Effects of Dehydroepiandrosterone Are Related to
Up-regulation of Thioredoxin in SH-SY5Y Cells
Jing GAO*, Hui-Ying SUN,
Zeng-Rong ZHU, Zhen DING, and Li ZHU1
School of
Medicine, School of Life Sciences, Nanjing University, Nanjing 210093, China;
1Institute of Nautical Medicine, Nantong
University, Nantong 226001, China
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 (10100
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 mM), 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.
Key words dehydroepiandrosterone (DHEA);
thioredoxin (Trx); H2O2; SH-SY5Y cell
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Received: November 17, 2004 Accepted: January 6,
2005
*Corresponding author: Tel, 86-25-83593374; Fax, 86-25-83686559;
E-mail, [email protected]