Publication: Hepatic response to chronic hypoxia in experimental rat model through HIF-1 alpha, activator protein-1 and NF-kappa B
Authors
Lau, Thomas Y.H. ; Xiao, Jia ; Liong, Emily C. ; Liao, Linchuan ; Leung, Tung-Ming ; Nanji, Amin A. ; Fung, Man Lung ; Tipoe, George L.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Chronic liver diseases are commonly
associated with tissue hypoxia that may cause
inflammation, oxidative stress, liver cell injury and
increased nuclear transcriptional regulation. The hepatic
response to chronic hypoxia at the molecular level has
not yet been clearly understood until now. The aim of
this study is to investigate whether nuclear transcription
factors [hypoxia-inducible factor-1 (HIF-1α), activator
protein-1 (AP-1), nuclear factor-kappa B (NF-κB)]
exhibit activity changes during hepatic response to
chronic hypoxia. Blood and liver samples were collected
from adult Sprague-Dawley rats living in atmospheric
air or 10% oxygen for four weeks. Levels of serum
alanine aminotransferase (ALT), 8-isoprostane and
nitrotyrosine were measured. The activities of nuclear
transcription factors and the expression of downstream
genes (iNOS, eNOS, ET-1 and VEGF) were measured
using RT-PCR, Western blotting and Gel shift analysis.
Results showed that serum ALT level, 8-isoprostane
level and formation of nitrotyrosine were within normal
range at all time-points. In the hypoxic liver, DNAbinding
activities of HIF-1α, NF-κB and AP-1 increased
significantly. Expression levels of iNOS, VEGF and ET1
progressively increased from day 7 to day 28. eNOS
was also elevated in the hypoxic liver. In conclusion, our
study suggests that increased activity of HIF-1α, AP-1
and NF-κB may partly play a significant role in the
hepatic response to oxidative stress and liver injury
under chronic hypoxia. The increased expression of
VEGF, ET-1, iNOS and eNOS may be partly due to the
compensatory mechanism in the vascular beds of the
liver in response to chronic hypoxia.
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Citation
Histology and histopathology, Vol. 28, n.º 4 (2013)
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