Administration of an aldose reductase inhibitor, ONO-2235, to streptozotocin-diabetic mice restores reductions of DRG neuronal attachment to extracellular matrix proteins in vitro.
Attachments of cultured dorsal root ganglion (DRG) neurons to the extracellular matrix (ECM) proteins (type I and IV collagens, laminin and fibronectin) and the adhesion ligand arginine-glycine-aspartic acid (RGD) were impaired in mice 2 weeks after the induction of diabetes by streptozotocin (STZ). However, administration of the aldose reductase inhibitor, ONO-2235, to the STZ-diabetic mice for 1 week restored DRG neuronal attachment to the ECM proteins and RGD to a level close to normal mice. These results suggest that activation of the aldose reductase and subsequent metabolic disorders in diabetic animals may play an important role in detrimental alterations of the neuronal cell-surface receptors for the ECM proteins.
Sango
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K
Division of Geriatric Health and Nutrition, National Institute of Health and Nutrition, Tokyo, Japan. kazsango@nih.go.jp
Horie
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H
Inoue
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D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000502:physiology; D005727:Ganglia, Spinal / Q000503:physiopathology*; D007797:Laminin / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides; D012016:Reference Values; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053778:Thiazolidines
D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D009842:Oligopeptides; D053778:Thiazolidines; C038131:epalrestat; C047981:arginyl-glycyl-aspartic acid; D012236:Rhodanine; D003094:Collagen; D000449:Aldehyde Reductase