Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H

quinone oxidoreductase 1 during cholestasis

Lauren M. Aleksunes, Angela L. Slitt, Jonathan M. Maher, Matthew Z. Dieter, Tamara R. Knight, Michael Goedken, Nathan J Cherrington, Jefferson Y. Chan, Curtis D. Klaassen, José E. Manautou

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Bile duct ligation (BDL) causes hepatocellular oxidative stress and injury. The transcription factor nuclear factor-E2-related factor (Nrf2) induces expression of numerous genes including NAD(P)H:quinone oxidoreductase 1 (Nqo1) during periods of oxidative stress. Therefore, we hypothesized that BDL increases liver expression of mouse antioxidant genes in an Nrf2-dependent manner. BDL or sham surgeries were performed on male C57BL/6, Nrf2-null, and wild-type mice. Livers were collected at 1, 3, and 7 days after surgery for analysis of messenger ribonucleic acid (mRNA) levels of Nrf2-responsive genes as well as Nqo1 protein and activity. BDL increased mRNA expression of multiple Nrf2 genes in mouse liver, compared to sham-operated controls. Follow-up studies investigating protein expression, enzyme activity, and Nrf2 dependency were limited to Nqo1. Nqo1 protein expression and activity in mouse livers was increased 2- to 3-, and 4- to 5-fold at 3 and 7 days after BDL, respectively. Studies also showed that BDL increases Nqo1 mRNA, protein expression, and enzyme activity in livers from wild-type mice, but not in Nrf2-null mice. In conclusion, expression of Nrf2-dependent genes is increased during cholestasis. These studies also demonstrate that Nqo1 expression and activity in mouse liver are induced via an Nrf2-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)356-363
Number of pages8
JournalCell Stress and Chaperones
Volume11
Issue number4
DOIs
StatePublished - Dec 2006

Fingerprint

NF-E2-Related Factor 2
Cholestasis
Liver
NAD
Ducts
Bile Ducts
Oxidoreductases
Ligation
Genes
Oxidative stress
Enzyme activity
RNA
Surgery
Proteins
Oxidative Stress
Enzymes
benzoquinone
Ambulatory Surgical Procedures
Transcription Factors
Antioxidants

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Aleksunes, L. M., Slitt, A. L., Maher, J. M., Dieter, M. Z., Knight, T. R., Goedken, M., ... Manautou, J. E. (2006). Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H: quinone oxidoreductase 1 during cholestasis. Cell Stress and Chaperones, 11(4), 356-363. https://doi.org/10.1379/CSC-217.1

Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H : quinone oxidoreductase 1 during cholestasis. / Aleksunes, Lauren M.; Slitt, Angela L.; Maher, Jonathan M.; Dieter, Matthew Z.; Knight, Tamara R.; Goedken, Michael; Cherrington, Nathan J; Chan, Jefferson Y.; Klaassen, Curtis D.; Manautou, José E.

In: Cell Stress and Chaperones, Vol. 11, No. 4, 12.2006, p. 356-363.

Research output: Contribution to journalArticle

Aleksunes, LM, Slitt, AL, Maher, JM, Dieter, MZ, Knight, TR, Goedken, M, Cherrington, NJ, Chan, JY, Klaassen, CD & Manautou, JE 2006, 'Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H: quinone oxidoreductase 1 during cholestasis', Cell Stress and Chaperones, vol. 11, no. 4, pp. 356-363. https://doi.org/10.1379/CSC-217.1
Aleksunes, Lauren M. ; Slitt, Angela L. ; Maher, Jonathan M. ; Dieter, Matthew Z. ; Knight, Tamara R. ; Goedken, Michael ; Cherrington, Nathan J ; Chan, Jefferson Y. ; Klaassen, Curtis D. ; Manautou, José E. / Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H : quinone oxidoreductase 1 during cholestasis. In: Cell Stress and Chaperones. 2006 ; Vol. 11, No. 4. pp. 356-363.
@article{2cbd8b624c3446cf975044488c0dd155,
title = "Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H: quinone oxidoreductase 1 during cholestasis",
abstract = "Bile duct ligation (BDL) causes hepatocellular oxidative stress and injury. The transcription factor nuclear factor-E2-related factor (Nrf2) induces expression of numerous genes including NAD(P)H:quinone oxidoreductase 1 (Nqo1) during periods of oxidative stress. Therefore, we hypothesized that BDL increases liver expression of mouse antioxidant genes in an Nrf2-dependent manner. BDL or sham surgeries were performed on male C57BL/6, Nrf2-null, and wild-type mice. Livers were collected at 1, 3, and 7 days after surgery for analysis of messenger ribonucleic acid (mRNA) levels of Nrf2-responsive genes as well as Nqo1 protein and activity. BDL increased mRNA expression of multiple Nrf2 genes in mouse liver, compared to sham-operated controls. Follow-up studies investigating protein expression, enzyme activity, and Nrf2 dependency were limited to Nqo1. Nqo1 protein expression and activity in mouse livers was increased 2- to 3-, and 4- to 5-fold at 3 and 7 days after BDL, respectively. Studies also showed that BDL increases Nqo1 mRNA, protein expression, and enzyme activity in livers from wild-type mice, but not in Nrf2-null mice. In conclusion, expression of Nrf2-dependent genes is increased during cholestasis. These studies also demonstrate that Nqo1 expression and activity in mouse liver are induced via an Nrf2-dependent mechanism.",
author = "Aleksunes, {Lauren M.} and Slitt, {Angela L.} and Maher, {Jonathan M.} and Dieter, {Matthew Z.} and Knight, {Tamara R.} and Michael Goedken and Cherrington, {Nathan J} and Chan, {Jefferson Y.} and Klaassen, {Curtis D.} and Manautou, {Jos{\'e} E.}",
year = "2006",
month = "12",
doi = "10.1379/CSC-217.1",
language = "English (US)",
volume = "11",
pages = "356--363",
journal = "Cell Stress and Chaperones",
issn = "1355-8145",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H

T2 - quinone oxidoreductase 1 during cholestasis

AU - Aleksunes, Lauren M.

AU - Slitt, Angela L.

AU - Maher, Jonathan M.

AU - Dieter, Matthew Z.

AU - Knight, Tamara R.

AU - Goedken, Michael

AU - Cherrington, Nathan J

AU - Chan, Jefferson Y.

AU - Klaassen, Curtis D.

AU - Manautou, José E.

PY - 2006/12

Y1 - 2006/12

N2 - Bile duct ligation (BDL) causes hepatocellular oxidative stress and injury. The transcription factor nuclear factor-E2-related factor (Nrf2) induces expression of numerous genes including NAD(P)H:quinone oxidoreductase 1 (Nqo1) during periods of oxidative stress. Therefore, we hypothesized that BDL increases liver expression of mouse antioxidant genes in an Nrf2-dependent manner. BDL or sham surgeries were performed on male C57BL/6, Nrf2-null, and wild-type mice. Livers were collected at 1, 3, and 7 days after surgery for analysis of messenger ribonucleic acid (mRNA) levels of Nrf2-responsive genes as well as Nqo1 protein and activity. BDL increased mRNA expression of multiple Nrf2 genes in mouse liver, compared to sham-operated controls. Follow-up studies investigating protein expression, enzyme activity, and Nrf2 dependency were limited to Nqo1. Nqo1 protein expression and activity in mouse livers was increased 2- to 3-, and 4- to 5-fold at 3 and 7 days after BDL, respectively. Studies also showed that BDL increases Nqo1 mRNA, protein expression, and enzyme activity in livers from wild-type mice, but not in Nrf2-null mice. In conclusion, expression of Nrf2-dependent genes is increased during cholestasis. These studies also demonstrate that Nqo1 expression and activity in mouse liver are induced via an Nrf2-dependent mechanism.

AB - Bile duct ligation (BDL) causes hepatocellular oxidative stress and injury. The transcription factor nuclear factor-E2-related factor (Nrf2) induces expression of numerous genes including NAD(P)H:quinone oxidoreductase 1 (Nqo1) during periods of oxidative stress. Therefore, we hypothesized that BDL increases liver expression of mouse antioxidant genes in an Nrf2-dependent manner. BDL or sham surgeries were performed on male C57BL/6, Nrf2-null, and wild-type mice. Livers were collected at 1, 3, and 7 days after surgery for analysis of messenger ribonucleic acid (mRNA) levels of Nrf2-responsive genes as well as Nqo1 protein and activity. BDL increased mRNA expression of multiple Nrf2 genes in mouse liver, compared to sham-operated controls. Follow-up studies investigating protein expression, enzyme activity, and Nrf2 dependency were limited to Nqo1. Nqo1 protein expression and activity in mouse livers was increased 2- to 3-, and 4- to 5-fold at 3 and 7 days after BDL, respectively. Studies also showed that BDL increases Nqo1 mRNA, protein expression, and enzyme activity in livers from wild-type mice, but not in Nrf2-null mice. In conclusion, expression of Nrf2-dependent genes is increased during cholestasis. These studies also demonstrate that Nqo1 expression and activity in mouse liver are induced via an Nrf2-dependent mechanism.

UR - http://www.scopus.com/inward/record.url?scp=33947588378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947588378&partnerID=8YFLogxK

U2 - 10.1379/CSC-217.1

DO - 10.1379/CSC-217.1

M3 - Article

VL - 11

SP - 356

EP - 363

JO - Cell Stress and Chaperones

JF - Cell Stress and Chaperones

SN - 1355-8145

IS - 4

ER -