Immunodetection of aldose reductase in normal and diseased human liver

K E Brown; K A Broadhurst; M M Mathahs; R D Kladney; C J Fimmel; S K Srivastava; E M Brunt

doi:10.14670/HH-20.429

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Immunodetection of aldose reductase in normal and diseased human liver

Journal article

Peer reviewed

Immunodetection of aldose reductase in normal and diseased human liver

K E Brown, K A Broadhurst, M M Mathahs, R D Kladney, C J Fimmel, S K Srivastava and E M Brunt

Histology and histopathology, Vol.20(2), pp.429-436

04/2005

DOI: 10.14670/HH-20.429

PMID: 15736047

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Abstract

Aldose reductase is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway that is implicated in the complications of diabetes. Aldose reductase appears to be involved in a variety of disease states other than diabetes, presumably due to its ability to catalyze the reduction of a broad spectrum of aldehydes, including some cytotoxic products of lipid peroxidation. Although the data regarding expression of aldose reductase in normal liver are conflicting, prior studies have suggested that the enzyme may be induced in diseased liver. The goal of these studies was to characterize expression of aldose reductase in normal and diseased human liver, using RT-PCR, Western analysis and immunohistochemistry. Aldose reductase transcripts and protein were detected at low levels in control human livers. In contrast, levels of aldose reductase mRNA and protein were increased in chronically diseased human livers. Immunohistochemistry demonstrated localization of aldose reductase in sinusoidal lining cells; dual immunofluorescence confocal microscopy with the macrophage marker, CD68, confirmed that the aldose reductase-positive sinusoidal lining cells were Kupffer cells. Abundant aldose reductase-positive, CD68-positive cells were present in the fibrous septa of cirrhotic livers, accounting for the increase in immunoreactive aldose reductase in diseased livers. Immunostaining of human lung, spleen and lymph node revealed that macrophages in those tissues also express aldose reductase. These data are the first to demonstrate that aldose reductase is expressed by human macrophages in various tissues and suggest that this enzyme may play a role in immune or inflammatory processes.

Immunohistochemistry

Gene Expression

Kupffer Cells - pathology

Aldehyde Reductase - genetics

Liver - enzymology

Macrophages - pathology

Humans

RNA, Messenger - genetics

DNA, Complementary - genetics

Liver Diseases - pathology

RNA, Messenger - metabolism

Reverse Transcriptase Polymerase Chain Reaction

Case-Control Studies

Kupffer Cells - enzymology

Antigens, CD - metabolism

Macrophages - enzymology

Antigens, Differentiation, Myelomonocytic - metabolism

Base Sequence

Liver Diseases - enzymology

Aldehyde Reductase - metabolism

Liver - cytology

Details

Title: Subtitle: Immunodetection of aldose reductase in normal and diseased human liver
Creators: K E Brown - Iowa City Veterans Administration Medical Center, Iowa City, IA, USA. kyle-brown@uiowa.edu
K A Broadhurst
M M Mathahs
R D Kladney
C J Fimmel
S K Srivastava
E M Brunt
Resource Type: Journal article
Publication Details: Histology and histopathology, Vol.20(2), pp.429-436
Publisher: Spain
DOI: 10.14670/HH-20.429
PMID: 15736047
ISSN: 0213-3911
eISSN: 1699-5848
Language: English
Date published: 04/2005
Academic Unit: Gastroenterology and Hepatology; Radiation Oncology; Internal Medicine
Record Identifier: 9984047642602771

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