Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction

Autor: Todd E. Morgan, William G. Willmore, Skye McBride, Nikolai L. Chepelev, Hongqiao Zhang, Henry Jay Forman, Honglei Liu, Andrew J. Seal, Kelvin J.A. Davies, Caleb E. Finch
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
Aging
Clinical Biochemistry
GCLM
modifier subunit of GCL
Biochemistry
Antioxidants
Nrf1
nuclear factor-erythroid 2 p45 subunit-related factor 1
Gene Knockout Techniques
Mice
HBE1
human bronchial epithelial cells
0302 clinical medicine
Gene expression
Protein Isoforms
GCL
glutamate cysteine ligase
NRF1
Lung
lcsh:QH301-705.5
Regulation of gene expression
0303 health sciences
lcsh:R5-920
biology
Nuclear Respiratory Factor 1
GCLM
Phase II genes
GCLC
HO-1
heme oxygenase
NF-E2 Transcription Factor
p45 Subunit
GCLC
catalytic subunit of GCL
lcsh:Medicine (General)
Research Paper
Gene isoform
Glutamate-Cysteine Ligase
Air pollution
Bronchi
Nrf2
nuclear factor-erythroid 2 p45 subunit-related factor 2
Response Elements
Nrf2
EpRE
electrophile response element
Cell Line
Nrf1
ER
endoplasmic reticulum
03 medical and health sciences
nPM
nanoparticulate air pollution
Glutamate cysteine ligase
Animals
Humans
Enzyme inducer
Transcription factor
030304 developmental biology
Electrophile response element
Organic Chemistry
Epithelial Cells
Molecular biology
Mice
Inbred C57BL
HEK293 Cells
Gene Expression Regulation
lcsh:Biology (General)
biology.protein
Particulate Matter
030217 neurology & neurosurgery
Zdroj: Redox Biology, Vol 1, Iss 1, Pp 183-189 (2013)
Redox Biology
ISSN: 2213-2317
Popis: Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) regulated expression of multiple antioxidant and cytoprotective genes through the electrophile responsive element (EpRE) is well established, interaction of Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well understood. Due to either proteolysis or alternative translation, Nrf1 has been found as proteins of varying size, p120, p95, and p65, which have been described as either activators of EpRE or competitive inhibitors of Nrf2. We investigated the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and modifier subunits of glutamate cysteine ligase (GCLC and GCLM) as models and explored the potential role of Nrf1 in altering their expression in aging and upon chronic exposure to airborne nano-sized particulate matter (nPM). Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1) cells. Overexpression Nrf2 in combination with either p120 or p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase activity. All known forms of Nrf1 protein, remained unchanged in the lungs of mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE activity in vitro, whereas the precise role of Nrf1 in vivo requires further investigations. We conclude that Nrf1 may not be directly responsible for the loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes observed in aged animals.
Highlights ► Nrf1 knockout increased GCLC and GCLM expression in human bronchial epithelial cells. ► Overexpressed Nrf1 forms p120 or p65 increased GCLC- and GLCM-EpRE luciferase activity. ► Overexpressed Nrf2 competes with Nrf1 forms. ► Nrf1 forms are unchanged in the lungs of mice by age. ► Nrf1 forms are unchanged in exposure to nanoparticulate air pollution.
Databáze: OpenAIRE
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