The role of aldose reductase in sugar cataract formation: Aldose reductase plays a key role in lens epithelial cell death (apoptosis)

Masatoshi Murata, Nobuo Ohta, Shinichi Sakurai, Shahabuddin Alam, Jen Yue Tsai, Peter F. Kador, Sanai Sato

Research output: Contribution to journalArticle

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Abstract

Since aldose reductase is localized primarily in lens epithelial cells, osmotic insults induced by the accumulation of sugar alcohols occur first in these cells. To determine whether the accumulation of sugar alcohols can induce lens epithelial cell death, galactose-induced apoptosis has been investigated in dog lens epithelial cells. Dog lens epithelial cells were cultured in Dulbecco's modified Eagle's mimimum essential medium (DMEM) supplemented with 20% fetal calf serum (FCS). After reaching confluence at fifth passage, the medium was replaced with the same DMEM medium containing 50 mM D-galactose and the cells were cultured for an additional 2 weeks. Almost all of the cells cultured in galactose medium were stained positively for apoptosis with the terminal deoxynucleotidyl transferance-mediated biotin-dUTP nick end labeling (TUNEL) technique. Agarose gel electrophoresis of these cells displayed obvious DNA fragmentation, known as a ladder formation. All of these apoptotic changes were absent in similar cells cultured in galactose medium containing 1 μM of the aldose reductase inhibitor AL 1576. Addition of AL 1576 also reduced the cellular galactitol levels from 123 ± 10 μg/106 cells (n = 5) to 3.9 ± 1.9 μg/106 cells (n = 5). These observations confirm that galactose induced apoptosis occurs in dog lens epithelial cells. Furthermore, the prevention of apoptosis by an aldose reductase inhibitor suggests that this apoptosis is linked to the accumulation of sugar alcohols.

Original languageEnglish (US)
Pages (from-to)617-625
Number of pages9
JournalChemico-Biological Interactions
Volume130-132
DOIs
StatePublished - Jan 30 2001

Fingerprint

Aldehyde Reductase
Cell death
Galactose
Sugars
Cataract
Lenses
Sugar Alcohols
Cell Death
Epithelial Cells
Apoptosis
Cultured Cells
Eagles
Dogs
Galactitol
Agar Gel Electrophoresis
Ladders
DNA Fragmentation
Biotin
Electrophoresis
Sepharose

Keywords

  • Aldose reductase
  • Apoptosis
  • Dog
  • Lens epithelial cells
  • Sugar cataract

ASJC Scopus subject areas

  • Toxicology

Cite this

The role of aldose reductase in sugar cataract formation : Aldose reductase plays a key role in lens epithelial cell death (apoptosis). / Murata, Masatoshi; Ohta, Nobuo; Sakurai, Shinichi; Alam, Shahabuddin; Tsai, Jen Yue; Kador, Peter F.; Sato, Sanai.

In: Chemico-Biological Interactions, Vol. 130-132, 30.01.2001, p. 617-625.

Research output: Contribution to journalArticle

Murata, Masatoshi ; Ohta, Nobuo ; Sakurai, Shinichi ; Alam, Shahabuddin ; Tsai, Jen Yue ; Kador, Peter F. ; Sato, Sanai. / The role of aldose reductase in sugar cataract formation : Aldose reductase plays a key role in lens epithelial cell death (apoptosis). In: Chemico-Biological Interactions. 2001 ; Vol. 130-132. pp. 617-625.
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