Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H2O2-induced oxidative stress.
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 5alpha- 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-kappaB), 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-kappaB in mouse ES cells.
Lee
Mi Na
MN
Department of Urology, Chonnam National University Medical School, Gwangju 501-746, Korea.
Lee
Sang Hun
SH
Lee
Min Young
MY
Kim
Yun Hee
YH
Park
Jae Hong
JH
Ryu
Jung Min
JM
Yun
Seung Pil
SP
Lee
Yu Jin
YJ
Kim
Mi Ok
MO
Park
Kwangsung
K
Han
Ho Jae
HJ
D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013196:Dihydrotestosterone; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D013936:Thymidine