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KMID : 0893420080090030247
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Journal of Veterinary Science
2008 Volume.9 No. 3 p.247 ~ p.256
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Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H2O2-induced oxidative stress
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Lee Mi-Na
Lee Sang-Hoon
Lee Min-Young
Kim Yun-Hee
Park Jae-Hong
Ryu Jung-Min
Yun Seung-Pil
Lee Yu-Jin
Kim Mi-Ok
Park Kwang-Sung
Han Ho-Jae
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Abstract
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Oxidative stresses induced by reactive oxygen species (ROS) have been shown to be involved in several physiological and pathophysiological processes, such as cell proliferation and differentiation. Steroid hormones can protect cells against apoptosis or induce cell proliferation by several mechanisms. Among androgenic hormones, dihydrotestosterone (DHT) is generated by a 5α- reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol, therefore DHT is considered a pure androgenic steroid. This study was conducted to examine the effect of DHT (10-7 M) on H2O2 (10-3 M) -induced injuries in mouse embryonic stem (ES) cells. H2O2 induced ROS generation and increased lipid peroxide formation and DNA fragmentation. These effects of H2O2 were inhibited by pretreatment with DHT. H2O2 also increased the phosphorylation of p38 MAPK, SAPK/JNK and nuclear factor kappa B (NF-κB), but DHT blocked these effects. Moreover, H2O2 decreased DNA synthesis and the levels of cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were inhibited by pretreatment with DHT. In conclusion, DHT may partially prevent H2O2-induced cell injury through inhibition of ROS and ROS-induced activation of p38 MAPK, SAPK/JNK and NF-κB in mouse ES cells.
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KEYWORD
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DHT, dihydrotestosterone, H2O2, mouse ES cell, oxidative stress
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