Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H(2)O(2)-induced oxidative stress.
- Author:
Mi Na LEE
1
;
Sang Hun LEE
;
Min Young LEE
;
Yun Hee KIM
;
Jae Hong PARK
;
Jung Min RYU
;
Seung Pil YUN
;
Yu Jin LEE
;
Mi Ok KIM
;
Kwangsung PARK
;
Ho Jae HAN
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: DHT; dihydrotestosterone; H(2)O(2); mouse ES cell; oxidative stress
- MeSH: Animals; Blotting, Western; Cell Culture Techniques; Cells, Cultured; Dihydrotestosterone/*pharmacology; Embryonic Stem Cells/cytology/*drug effects/pathology/*physiology; Enzyme Activation; Hydrogen Peroxide/*pharmacology; Mice; Models, Biological; NF-kappa B/drug effects/metabolism; Oxidative Stress/drug effects/*physiology; Reactive Oxygen Species/metabolism; Signal Transduction/drug effects; Thymidine/metabolism; p38 Mitogen-Activated Protein Kinases/drug effects/metabolism
- From:Journal of Veterinary Science 2008;9(3):247-256
- CountryRepublic of Korea
- Language:English
- Abstract: 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 H(2)O(2) (10(-3) M) -induced injuries in mouse embryonic stem (ES) cells. H(2)O(2) induced ROS generation and increased lipid peroxide formation and DNA fragmentation. These effects of H(2)O(2) were inhibited by pretreatment with DHT. H(2)O(2) also increased the phosphorylation of p38 MAPK, SAPK/JNK and nuclear factor kappa B (NF-kappaB), but DHT blocked these effects. Moreover, H(2)O(2) 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 H(2)O(2) were inhibited by pretreatment with DHT. In conclusion, DHT may partially prevent H(2)O(2)-induced cell injury through inhibition of ROS and ROS-induced activation of p38 MAPK, SAPK/JNK and NF-kappaB in mouse ES cells.
