Polyol pathway-dependent osmotic and oxidative stresses in aldose reductase-mediated apoptosis in human lens epithelial cells: Role of AOP2

E. Kubo, T. Urakami, N. Fatma, Y. Akagi, Dhirendra P. Singh

Research output: Contribution to journalArticle

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Abstract

Aldose reductase (AR) has been implicated as a major contributor to the pathogenesis of diabetic cataracts. AR activation generates osmotic and oxidative stresses via the polyol pathway and induces cell death signals. Antioxidant protein 2 (AOP2) protects cells from oxidative stress. We investigated the effect of AR overexpression on polyol accumulation and on hyperglycemic oxidative stress and osmotic stress, as well as the effects of these stresses on human lens epithelial cell (hLEC) survival. hLECs overexpressing the AR became apoptotic during hyperglycemia and showed elevated levels of intracellular polyols. Glutathione and AOP2 levels were significantly decreased in these cells. Interestingly, supply of AOP2 and/or the AR inhibitor fidarestat protected the cells against hyperglycemia-induced death. Overexpression of AR increased osmotic and oxidative stresses, resulting in increased apoptosis in hLECs. Because AOP2 protects hyperglycemia-induced hLEC apoptosis, this molecule may have the potential to prevent hyperglycemia- mediated complications in diabetes.

Original languageEnglish (US)
Pages (from-to)1050-1056
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number4
DOIs
StatePublished - Feb 20 2004

Fingerprint

Aldehyde Reductase
Oxidative stress
Osmotic Pressure
Lenses
Oxidative Stress
Antioxidants
Epithelial Cells
Apoptosis
Hyperglycemia
Proteins
Cell death
Diabetes Complications
Medical problems
Cataract
Glutathione
polyol
Cell Survival
Cell Death
Chemical activation
Molecules

Keywords

  • Aldose reductase
  • Antioxidant protein 2
  • Apoptosis
  • Diabetic cataract

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Polyol pathway-dependent osmotic and oxidative stresses in aldose reductase-mediated apoptosis in human lens epithelial cells : Role of AOP2. / Kubo, E.; Urakami, T.; Fatma, N.; Akagi, Y.; Singh, Dhirendra P.

In: Biochemical and Biophysical Research Communications, Vol. 314, No. 4, 20.02.2004, p. 1050-1056.

Research output: Contribution to journalArticle

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