Aldose reductase mediates cytotoxic signals of hyperglycemia and TNF‐α in human lens epithelial cells

Abstract

SPECIFIC AIMAlthough the development of secondary diabetic complications is associated with increased apoptosis in several target tissues, the mechanisms by which diabetes induces cell death remain unclear. The aim of this study was to examine the role of the aldose reductase (AR), an enzyme that metabolizes excess glucose to sorbitol and contributes to the osmotic and oxidative effects of diabetes in cell death induced by two main instigators of diabetic injury: high glucose and TNF-α.PRINCIPAL FINDINGS1. Inhibition of AR attenuates high glucose and TNF-α-induced apoptosis in HLECIncubation of the serum-starved transformed human lens epithelial cells δ-B3 (HLEC) with high glucose (50 mM) or TNF-α (2 nm) for 24 h decreased cell growth, viability, and DNA synthesis ([3H]-thymidine incorporation) and increased caspase-3 activity, nuclear fragmentation and degradation of nucleosomal histones measured using Roche’s Cell Death ELISA kit), consistent with increased apoptosis. Preincubation of these cells with t...