Abstract
Original language | English |
---|---|
Pages (from-to) | 761-770 |
Number of pages | 10 |
Journal | Biochemical Journal |
Volume | 449 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2013 |
Externally published | Yes |
Keywords
- Hyperbilirubinaemia
- Inhibitor
- Lipopolysaccharide (LPS)
- Nuclear factor κB (NF-κB)
- Promoter
- UDP-glucuronosyltransferase 1A1 (UGT1A1)
- glucuronosyltransferase 1A1
- immunoglobulin enhancer binding protein
- lipopolysaccharide
- animal experiment
- article
- binding site
- cancer cell culture
- chromatin immunoprecipitation
- controlled study
- disease association
- down regulation
- enzyme activation
- gel mobility shift assay
- human
- human cell
- hyperbilirubinemia
- inflammation
- mouse
- nonhuman
- pathogenesis
- priority journal
- protein expression
- real time polymerase chain reaction
- reverse transcription polymerase chain reaction
- Western blotting
- Animals
- Base Sequence
- Binding Sites
- Cell Line
- DNA, Complementary
- Down-Regulation
- Glucuronosyltransferase
- Hep G2 Cells
- Humans
- Hyperbilirubinemia
- Inflammation
- Lipopolysaccharides
- Liver
- Mice
- Mice, Inbred C57BL
- Models, Biological
- NF-kappa B
- Promoter Regions, Genetic
- RNA, Messenger
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In: Biochemical Journal, Vol. 449, No. 3, 2013, p. 761-770.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Nuclear factor κB down-regulates human UDP-glucuronosyltransferase 1A1: A novel mechanism involved in inflammation-associated hyperbilirubinaemia
AU - Shiu, Tzu-Yue
AU - Huang, Tien-Yu
AU - Huang, Shih-Ming
AU - Shih, Yu-Lueng
AU - Chu, Heng-Cheng
AU - Chang, Wei-Kuo
AU - Hsieh, Tsai-Yuan
N1 - 被引用次數:1 Export Date: 22 March 2016 CODEN: BIJOA 通訊地址: Shiu, T.-Y.; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; 電子郵件: [email protected] 化學物質/CAS: DNA, Complementary; Glucuronosyltransferase, 2.4.1.17; Lipopolysaccharides; NF-kappa B; RNA, Messenger; bilirubin uridine-diphosphoglucuronosyl transferase 1A1, 2.4.1.- 參考文獻: Tukey, R.H., Strassburg, C.P., Human UDP-glucuronosyltransferases: Metabolism, expression, and disease (2000) Annual Review of Pharmacology and Toxicology, 40, pp. 581-616. , DOI 10.1146/annurev.pharmtox.40.1.581; Van Es, H.H.G., Bout, A., Liu, J., Anderson, L., Duncan, A.M.V., Bosma, P., Oude, E.R., Schurr, E., Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37 (1993) Cytogenetics and Cell Genetics, 63 (2), pp. 114-116; Mackenzie, P.I., Bock, K.W., Burchell, B., Guillemette, C., Ikushiro, S.-I., Iyanagi, T., Miners, J.O., Nebert, D.W., Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily (2005) Pharmacogenetics and Genomics, 15 (10), pp. 677-685; Nakamura, A., Nakajima, M., Yamanaka, H., Fujiwara, R., Yokoi, T., Expression of UGT1A and UGT2B mRNA in human normal tissues and various cell lines (2008) Drug Metab. 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Biol. Chem., 276, pp. 32008-32015
PY - 2013
Y1 - 2013
N2 - Jaundice or hyperbilirubinaemia is a common complication of sepsis. UGT1A1 (UDP-glucuronosyltransferase 1A1) is a critical gene for bilirubin metabolism and irinotecan detoxification. However, the molecular pathogenesis of hyperbilirubinaemia during inflammation needs to be further clarified. Human hepatic UGT1A1 expression was analysed by RT (reverse transcription)-PCR, qRT-PCR (quantitative real-time PCR) and Western blotting in response to LPS (lipopolysaccharide) stimulation. Transcription regulatory elements in the upstream promoter region of the human UGT1A1 gene were determined using EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation). The important role of the transcription regulatory element was examined using a luciferase assay, and was determined by qRT-PCR using a transcription factor activation inhibitor. LPS down-regulated the UGT1A1 mRNA expression in human hepatoma cell lines. A newly identified NF-κB (nuclear factor κB)-binding site was located on the upstream promoter region (-725/-716) of the human UGT1A1 gene. LPS-induced NF-κB activation and specific binding to the NF-κB-binding site can suppress human UGT1A1 promoter activity and human UGT1A1 expression. We demonstrated that LPS mediates the suppression of human UGT1A1 expression through specific binding of NF-κB to this newly identified NF-κB-binding site in the upstream promoter of the human UGT1A1 gene. The present study may partly explain the molecular pathogenesis of inflammation-associated hyperbilirubinaemia. © The Authors Journal compilation © 2013 Biochemical Society.
AB - Jaundice or hyperbilirubinaemia is a common complication of sepsis. UGT1A1 (UDP-glucuronosyltransferase 1A1) is a critical gene for bilirubin metabolism and irinotecan detoxification. However, the molecular pathogenesis of hyperbilirubinaemia during inflammation needs to be further clarified. Human hepatic UGT1A1 expression was analysed by RT (reverse transcription)-PCR, qRT-PCR (quantitative real-time PCR) and Western blotting in response to LPS (lipopolysaccharide) stimulation. Transcription regulatory elements in the upstream promoter region of the human UGT1A1 gene were determined using EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation). The important role of the transcription regulatory element was examined using a luciferase assay, and was determined by qRT-PCR using a transcription factor activation inhibitor. LPS down-regulated the UGT1A1 mRNA expression in human hepatoma cell lines. A newly identified NF-κB (nuclear factor κB)-binding site was located on the upstream promoter region (-725/-716) of the human UGT1A1 gene. LPS-induced NF-κB activation and specific binding to the NF-κB-binding site can suppress human UGT1A1 promoter activity and human UGT1A1 expression. We demonstrated that LPS mediates the suppression of human UGT1A1 expression through specific binding of NF-κB to this newly identified NF-κB-binding site in the upstream promoter of the human UGT1A1 gene. The present study may partly explain the molecular pathogenesis of inflammation-associated hyperbilirubinaemia. © The Authors Journal compilation © 2013 Biochemical Society.
KW - Hyperbilirubinaemia
KW - Inhibitor
KW - Lipopolysaccharide (LPS)
KW - Nuclear factor κB (NF-κB)
KW - Promoter
KW - UDP-glucuronosyltransferase 1A1 (UGT1A1)
KW - glucuronosyltransferase 1A1
KW - immunoglobulin enhancer binding protein
KW - lipopolysaccharide
KW - animal experiment
KW - article
KW - binding site
KW - cancer cell culture
KW - chromatin immunoprecipitation
KW - controlled study
KW - disease association
KW - down regulation
KW - enzyme activation
KW - gel mobility shift assay
KW - human
KW - human cell
KW - hyperbilirubinemia
KW - inflammation
KW - mouse
KW - nonhuman
KW - pathogenesis
KW - priority journal
KW - protein expression
KW - real time polymerase chain reaction
KW - reverse transcription polymerase chain reaction
KW - Western blotting
KW - Animals
KW - Base Sequence
KW - Binding Sites
KW - Cell Line
KW - DNA, Complementary
KW - Down-Regulation
KW - Glucuronosyltransferase
KW - Hep G2 Cells
KW - Humans
KW - Hyperbilirubinemia
KW - Inflammation
KW - Lipopolysaccharides
KW - Liver
KW - Mice
KW - Mice, Inbred C57BL
KW - Models, Biological
KW - NF-kappa B
KW - Promoter Regions, Genetic
KW - RNA, Messenger
U2 - 10.1042/BJ20121055
DO - 10.1042/BJ20121055
M3 - Article
SN - 0264-6021
VL - 449
SP - 761
EP - 770
JO - Biochemical Journal
JF - Biochemical Journal
IS - 3
ER -