Tags

Type your tag names separated by a space and hit enter

7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways.
Int J Mol Med. 2014 Apr; 33(4):964-70.IJ

Abstract

This study investigated the effect of 7,8-dihydroxyflavone (DHF) on the expression and activity of heme oxygenase-1 (HO-1), an enzyme with potent antioxidant properties, as well as the molecular mechanisms involved. DHF markedly upregulated HO-1 mRNA and protein expression in human keratinocytes (HaCaT cells), resulting in increased HO-1 activity. DHF also increased the protein level of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates HO-1 expression by binding to the antioxidant response element (ARE) within the HO-1 gene promoter, in a time-dependent manner. Moreover, DHF decreased the expression of Kelch-like ECH-associated protein 1, a repressor of Nrf2 activity, and induced the translocation of Nrf2 from the cytosol into the nucleus, thereby allowing its association with the ARE site. DHF activated extracellular-regulated kinase (ERK) and protein kinase B (PKB, Akt) in keratinocytes, while the ERK and Akt inhibitors attenuated DHF-enhanced Nrf2 and HO-1 expression. DHF also protected the keratinocytes against hydrogen peroxide- and ultraviolet B-induced oxidative damage, while HO-1, ERK and Akt inhibitors markedly suppressed DHF-mediated cytoprotection. Taken together, the results suggested that DHF activates ERK- and Akt-Nrf2 signaling cascades in HaCaT cells, leading to the upregulation of HO-1 and cytoprotection against oxidative stress.

Authors+Show Affiliations

Food and Nutrition, Duksung Women's University, Seoul 132-714, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.Food and Nutrition, Duksung Women's University, Seoul 132-714, Republic of Korea.Biospectrum Life Science Institute, Seongnam, Gyunggi Do 442‑13, Republic of Korea.Biospectrum Life Science Institute, Seongnam, Gyunggi Do 442‑13, Republic of Korea.Biospectrum Life Science Institute, Seongnam, Gyunggi Do 442‑13, Republic of Korea.Aging Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.

Pub Type(s)

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

Language

eng

PubMed ID

24503931

Citation

Ryu, Min Ju, et al. "7,8-Dihydroxyflavone Protects Human Keratinocytes Against Oxidative Stress-induced Cell Damage Via the ERK and PI3K/Akt-mediated Nrf2/HO-1 Signaling Pathways." International Journal of Molecular Medicine, vol. 33, no. 4, 2014, pp. 964-70.
Ryu MJ, Kang KA, Piao MJ, et al. 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. Int J Mol Med. 2014;33(4):964-70.
Ryu, M. J., Kang, K. A., Piao, M. J., Kim, K. C., Zheng, J., Yao, C. W., Cha, J. W., Chung, H. S., Kim, S. C., Jung, E., Park, D., Chae, S., & Hyun, J. W. (2014). 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. International Journal of Molecular Medicine, 33(4), 964-70. https://doi.org/10.3892/ijmm.2014.1643
Ryu MJ, et al. 7,8-Dihydroxyflavone Protects Human Keratinocytes Against Oxidative Stress-induced Cell Damage Via the ERK and PI3K/Akt-mediated Nrf2/HO-1 Signaling Pathways. Int J Mol Med. 2014;33(4):964-70. PubMed PMID: 24503931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. AU - Ryu,Min Ju, AU - Kang,Kyoung Ah, AU - Piao,Mei Jing, AU - Kim,Ki Cheon, AU - Zheng,Jian, AU - Yao,Cheng Wen, AU - Cha,Ji Won, AU - Chung,Ha Sook, AU - Kim,Sang Cheol, AU - Jung,Eunsun, AU - Park,Deokhoon, AU - Chae,Sungwook, AU - Hyun,Jin Won, Y1 - 2014/02/04/ PY - 2013/09/23/received PY - 2014/01/30/accepted PY - 2014/2/8/entrez PY - 2014/2/8/pubmed PY - 2014/10/22/medline SP - 964 EP - 70 JF - International journal of molecular medicine JO - Int J Mol Med VL - 33 IS - 4 N2 - This study investigated the effect of 7,8-dihydroxyflavone (DHF) on the expression and activity of heme oxygenase-1 (HO-1), an enzyme with potent antioxidant properties, as well as the molecular mechanisms involved. DHF markedly upregulated HO-1 mRNA and protein expression in human keratinocytes (HaCaT cells), resulting in increased HO-1 activity. DHF also increased the protein level of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates HO-1 expression by binding to the antioxidant response element (ARE) within the HO-1 gene promoter, in a time-dependent manner. Moreover, DHF decreased the expression of Kelch-like ECH-associated protein 1, a repressor of Nrf2 activity, and induced the translocation of Nrf2 from the cytosol into the nucleus, thereby allowing its association with the ARE site. DHF activated extracellular-regulated kinase (ERK) and protein kinase B (PKB, Akt) in keratinocytes, while the ERK and Akt inhibitors attenuated DHF-enhanced Nrf2 and HO-1 expression. DHF also protected the keratinocytes against hydrogen peroxide- and ultraviolet B-induced oxidative damage, while HO-1, ERK and Akt inhibitors markedly suppressed DHF-mediated cytoprotection. Taken together, the results suggested that DHF activates ERK- and Akt-Nrf2 signaling cascades in HaCaT cells, leading to the upregulation of HO-1 and cytoprotection against oxidative stress. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/24503931/78_Dihydroxyflavone_protects_human_keratinocytes_against_oxidative_stress_induced_cell_damage_via_the_ERK_and_PI3K/Akt_mediated_Nrf2/HO_1_signaling_pathways_ L2 - http://www.spandidos-publications.com/ijmm/33/4/964 DB - PRIME DP - Unbound Medicine ER -