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Estradiol-17beta protects against hypoxia-induced hepatocyte injury through ER-mediated upregulation of Bcl-2 as well as ER-independent antioxidant effects.
Cell Res. 2008 Apr; 18(4):491-9.CR

Abstract

Although many previous studies have suggested that estrogen functions as a cytoprotective agent under oxidative stress conditions, the underlying mechanism by which this effect is exerted remains to be elucidated. This study assessed the effects of estradiol-17beta (E(2)) (10(-8) M) on hypoxia-induced cell injury and its related signaling in primary cultured chicken hepatocytes. Hypoxic conditions were found to augment the level of DNA damage and to reduce cell viability and the level of [(3)H]-thymidine incorporation, and these phenomena were prevented through treatment with E(2). Hypoxia also increased caspase-3 expression, but showed no evidence of an influence on the expression of Bcl-2. However, E(2) induced an increase in the level of Bcl-2 expression under hypoxic conditions and reduced the level of caspase-3 expression. The effects of E(2) on Bcl-2 and caspase expression were blocked by ICI 182780 (E(2) receptor (ER) antagonist, 10(-7) M). In addition, hypoxia resulted in an increase in the intracellular reactive oxygen species (ROS) generated. These effects were blocked by E(2), but not by E(2)-BSA and ICI 182780. Hypoxia also activated p38 mitogen-activated protein kinase (MAPK), c-JUN N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and nuclear factor-kappaB (NF-kappaB). These effects were blocked by E(2), but not by ICI 182780. The inhibition of p38 MAPK and JNK/SAPK blocked NF-kappaB activation. In conclusion, E(2) was found to protect against hypoxia-induced cell injury in chicken hepatocytes through ER-mediated upregulation of Bcl-2 expression and through reducing the activity of ROS-dependent p38 MAPK, JNK/SAPK and NF-kappaB.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18379592

Citation

Lee, Min Young, et al. "Estradiol-17beta Protects Against Hypoxia-induced Hepatocyte Injury Through ER-mediated Upregulation of Bcl-2 as Well as ER-independent Antioxidant Effects." Cell Research, vol. 18, no. 4, 2008, pp. 491-9.
Lee MY, Jung SC, Lee JH, et al. Estradiol-17beta protects against hypoxia-induced hepatocyte injury through ER-mediated upregulation of Bcl-2 as well as ER-independent antioxidant effects. Cell Res. 2008;18(4):491-9.
Lee, M. Y., Jung, S. C., Lee, J. H., & Han, H. J. (2008). Estradiol-17beta protects against hypoxia-induced hepatocyte injury through ER-mediated upregulation of Bcl-2 as well as ER-independent antioxidant effects. Cell Research, 18(4), 491-9. https://doi.org/10.1038/cr.2008.42
Lee MY, et al. Estradiol-17beta Protects Against Hypoxia-induced Hepatocyte Injury Through ER-mediated Upregulation of Bcl-2 as Well as ER-independent Antioxidant Effects. Cell Res. 2008;18(4):491-9. PubMed PMID: 18379592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estradiol-17beta protects against hypoxia-induced hepatocyte injury through ER-mediated upregulation of Bcl-2 as well as ER-independent antioxidant effects. AU - Lee,Min Young, AU - Jung,Sun Chul, AU - Lee,Jang Hern, AU - Han,Ho Jae, PY - 2008/4/2/pubmed PY - 2008/4/25/medline PY - 2008/4/2/entrez SP - 491 EP - 9 JF - Cell research JO - Cell Res VL - 18 IS - 4 N2 - Although many previous studies have suggested that estrogen functions as a cytoprotective agent under oxidative stress conditions, the underlying mechanism by which this effect is exerted remains to be elucidated. This study assessed the effects of estradiol-17beta (E(2)) (10(-8) M) on hypoxia-induced cell injury and its related signaling in primary cultured chicken hepatocytes. Hypoxic conditions were found to augment the level of DNA damage and to reduce cell viability and the level of [(3)H]-thymidine incorporation, and these phenomena were prevented through treatment with E(2). Hypoxia also increased caspase-3 expression, but showed no evidence of an influence on the expression of Bcl-2. However, E(2) induced an increase in the level of Bcl-2 expression under hypoxic conditions and reduced the level of caspase-3 expression. The effects of E(2) on Bcl-2 and caspase expression were blocked by ICI 182780 (E(2) receptor (ER) antagonist, 10(-7) M). In addition, hypoxia resulted in an increase in the intracellular reactive oxygen species (ROS) generated. These effects were blocked by E(2), but not by E(2)-BSA and ICI 182780. Hypoxia also activated p38 mitogen-activated protein kinase (MAPK), c-JUN N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and nuclear factor-kappaB (NF-kappaB). These effects were blocked by E(2), but not by ICI 182780. The inhibition of p38 MAPK and JNK/SAPK blocked NF-kappaB activation. In conclusion, E(2) was found to protect against hypoxia-induced cell injury in chicken hepatocytes through ER-mediated upregulation of Bcl-2 expression and through reducing the activity of ROS-dependent p38 MAPK, JNK/SAPK and NF-kappaB. SN - 1748-7838 UR - https://www.unboundmedicine.com/medline/citation/18379592/Estradiol_17beta_protects_against_hypoxia_induced_hepatocyte_injury_through_ER_mediated_upregulation_of_Bcl_2_as_well_as_ER_independent_antioxidant_effects_ L2 - https://doi.org/10.1038/cr.2008.42 DB - PRIME DP - Unbound Medicine ER -