Immunodetection of aldose reductase in normal and diseased human liver

Kyle E. Brown, K. A. Broadhurst, M. M. Mathahs, R. D. Kladney, C. J. Fimmel, Satish Srivastava, E. M. Brunt

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)429-436
Number of pages8
JournalHistology and Histopathology
Volume20
Issue number2
StatePublished - Apr 2005

Fingerprint

Aldehyde Reductase
Liver Diseases
Macrophages
Liver
Enzymes
Immunohistochemistry
Kupffer Cells
Diabetes Complications
NADP
Fluorescence Microscopy
Aldehydes
Confocal Microscopy
Lipid Peroxidation
Proteins
Spleen

Keywords

  • 4-hydroxy-2-nonenal
  • Aldo-keto reductase
  • Kupffer cells
  • Macrophages
  • Polyol pathway

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Brown, K. E., Broadhurst, K. A., Mathahs, M. M., Kladney, R. D., Fimmel, C. J., Srivastava, S., & Brunt, E. M. (2005). Immunodetection of aldose reductase in normal and diseased human liver. Histology and Histopathology, 20(2), 429-436.

Immunodetection of aldose reductase in normal and diseased human liver. / Brown, Kyle E.; Broadhurst, K. A.; Mathahs, M. M.; Kladney, R. D.; Fimmel, C. J.; Srivastava, Satish; Brunt, E. M.

In: Histology and Histopathology, Vol. 20, No. 2, 04.2005, p. 429-436.

Research output: Contribution to journalArticle

Brown, KE, Broadhurst, KA, Mathahs, MM, Kladney, RD, Fimmel, CJ, Srivastava, S & Brunt, EM 2005, 'Immunodetection of aldose reductase in normal and diseased human liver', Histology and Histopathology, vol. 20, no. 2, pp. 429-436.
Brown KE, Broadhurst KA, Mathahs MM, Kladney RD, Fimmel CJ, Srivastava S et al. Immunodetection of aldose reductase in normal and diseased human liver. Histology and Histopathology. 2005 Apr;20(2):429-436.
Brown, Kyle E. ; Broadhurst, K. A. ; Mathahs, M. M. ; Kladney, R. D. ; Fimmel, C. J. ; Srivastava, Satish ; Brunt, E. M. / Immunodetection of aldose reductase in normal and diseased human liver. In: Histology and Histopathology. 2005 ; Vol. 20, No. 2. pp. 429-436.
@article{9f79eee9f54145e9a7956d9e5c0850c3,
title = "Immunodetection of aldose reductase in normal and diseased human liver",
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.",
keywords = "4-hydroxy-2-nonenal, Aldo-keto reductase, Kupffer cells, Macrophages, Polyol pathway",
author = "Brown, {Kyle E.} and Broadhurst, {K. A.} and Mathahs, {M. M.} and Kladney, {R. D.} and Fimmel, {C. J.} and Satish Srivastava and Brunt, {E. M.}",
year = "2005",
month = "4",
language = "English (US)",
volume = "20",
pages = "429--436",
journal = "Histology and Histopathology",
issn = "0213-3911",
publisher = "Histology and Histopathology",
number = "2",

}

TY - JOUR

T1 - Immunodetection of aldose reductase in normal and diseased human liver

AU - Brown, Kyle E.

AU - Broadhurst, K. A.

AU - Mathahs, M. M.

AU - Kladney, R. D.

AU - Fimmel, C. J.

AU - Srivastava, Satish

AU - Brunt, E. M.

PY - 2005/4

Y1 - 2005/4

N2 - 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.

AB - 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.

KW - 4-hydroxy-2-nonenal

KW - Aldo-keto reductase

KW - Kupffer cells

KW - Macrophages

KW - Polyol pathway

UR - http://www.scopus.com/inward/record.url?scp=16444379233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16444379233&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 429

EP - 436

JO - Histology and Histopathology

JF - Histology and Histopathology

SN - 0213-3911

IS - 2

ER -