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Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells.
J Cell Physiol. 2008 Jul; 216(1):269-75.JC

Abstract

Steroid hormones have been reported to activate various signal transducers that trigger a variety of cellular responses. Among these hormones, testosterone has been identified as an antioxidant that protects against cellular damage. Therefore, using mouse embryonic stem (ES) cells as a model system, this study evaluated the effects of dihydrotestosterone (DHT), a biologically active testosterone metabolite, on H2O2-induced apoptosis. H2O2 increased the release of lactate dehydrogenase (LDH) and DNA fragmentation but reduced the cell viability in a time-dependent manner (> or =8 h). Moreover, H2O2 decreased the level of DNA synthesis and the levels of the cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were inhibited by a pretreatment with DHT. However, a treatment with flutamide (androgen receptor inhibitor, 10(-3) M) abolished the protective effects of DHT. This result was supported by the presence of the androgen receptor in mouse ES cells. The activity of the antioxidant enzyme, catalase, was increased by the DHT treatment but not by a co-treatment with DHT and flutamide. Using CM-H(2)DCFDA (DCF-DA) for the detection of intracellular H2O2, DHT decreased the intracellular H2O2 levels but flutamide blocked this effect. H2O2 also increased the level of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation, which were inhibited by the DHT pretreatment. Catalase inhibited the effect of H2O2 on MAPKs and NF-kappaB. However, the flutamide treatment abolished the inhibitory effects of DHT on the H2O2-induced increase in the levels of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation. DHT inhibited the H2O2-induced increase in caspase-3 expression and decreased the level of Bcl-2 and the cellular inhibitor of apoptosis protein (cIAP)-2. These effects were abolished by the flutamide treatment. In conclusion, DHT prevents the H2O2-induced apoptotic cell death of mouse ES cells through the activation of catalase and the downregulation of p38 MAPK, JNK/SAPK, and NF-kappaB via the androgen receptor.

Authors+Show Affiliations

Department of Veterinary Physiology, BK21 Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18330893

Citation

Lee, Sang Hun, et al. "Effect of Dihydrotestosterone On Hydrogen Peroxide-induced Apoptosis of Mouse Embryonic Stem Cells." Journal of Cellular Physiology, vol. 216, no. 1, 2008, pp. 269-75.
Lee SH, Heo JS, Lee MY, et al. Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. J Cell Physiol. 2008;216(1):269-75.
Lee, S. H., Heo, J. S., Lee, M. Y., & Han, H. J. (2008). Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. Journal of Cellular Physiology, 216(1), 269-75. https://doi.org/10.1002/jcp.21402
Lee SH, et al. Effect of Dihydrotestosterone On Hydrogen Peroxide-induced Apoptosis of Mouse Embryonic Stem Cells. J Cell Physiol. 2008;216(1):269-75. PubMed PMID: 18330893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. AU - Lee,Sang Hun, AU - Heo,Jung Sun, AU - Lee,Min Young, AU - Han,Ho Jae, PY - 2008/3/12/pubmed PY - 2008/6/5/medline PY - 2008/3/12/entrez SP - 269 EP - 75 JF - Journal of cellular physiology JO - J Cell Physiol VL - 216 IS - 1 N2 - Steroid hormones have been reported to activate various signal transducers that trigger a variety of cellular responses. Among these hormones, testosterone has been identified as an antioxidant that protects against cellular damage. Therefore, using mouse embryonic stem (ES) cells as a model system, this study evaluated the effects of dihydrotestosterone (DHT), a biologically active testosterone metabolite, on H2O2-induced apoptosis. H2O2 increased the release of lactate dehydrogenase (LDH) and DNA fragmentation but reduced the cell viability in a time-dependent manner (> or =8 h). Moreover, H2O2 decreased the level of DNA synthesis and the levels of the cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were inhibited by a pretreatment with DHT. However, a treatment with flutamide (androgen receptor inhibitor, 10(-3) M) abolished the protective effects of DHT. This result was supported by the presence of the androgen receptor in mouse ES cells. The activity of the antioxidant enzyme, catalase, was increased by the DHT treatment but not by a co-treatment with DHT and flutamide. Using CM-H(2)DCFDA (DCF-DA) for the detection of intracellular H2O2, DHT decreased the intracellular H2O2 levels but flutamide blocked this effect. H2O2 also increased the level of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation, which were inhibited by the DHT pretreatment. Catalase inhibited the effect of H2O2 on MAPKs and NF-kappaB. However, the flutamide treatment abolished the inhibitory effects of DHT on the H2O2-induced increase in the levels of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation. DHT inhibited the H2O2-induced increase in caspase-3 expression and decreased the level of Bcl-2 and the cellular inhibitor of apoptosis protein (cIAP)-2. These effects were abolished by the flutamide treatment. In conclusion, DHT prevents the H2O2-induced apoptotic cell death of mouse ES cells through the activation of catalase and the downregulation of p38 MAPK, JNK/SAPK, and NF-kappaB via the androgen receptor. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/18330893/Effect_of_dihydrotestosterone_on_hydrogen_peroxide_induced_apoptosis_of_mouse_embryonic_stem_cells_ L2 - https://doi.org/10.1002/jcp.21402 DB - PRIME DP - Unbound Medicine ER -