The apoptotic death of neuroblastoma cells caused by serum from patients with insulin-dependent diabetes and neuropathy may be Fas-mediated.
Immunoglobulins from patients with diabetic neuropathy are toxic to neuroblastoma cells. The cell death has characteristics of apoptosis: condensed chromatin, shrunken cytoplasm, elevation of [Ca2+]i and DNA fragmentation. N1E-115 cell membranes contain Fas, a regulator of apoptosis that recently has been shown to be involved in pancreatic beta-cell destruction leading to diabetes. Fas-specific antibodies bind to the surface of N1E-115 cells and induce apoptosis. Serum from patients with diabetic neuropathy block Fas-antibody binding. We conclude that sera from patients with diabetic neuropathy contain an activator of Fas-regulated apoptosis that may contribute to the pathogenesis of diabetic neuropathy.
Pittenger
G L
GL
Department of Internal Medicine, Diabetes Institutes, Eastern Virginia Medical School, Norfolk 23510, USA. glp@dil.evms.edu
Liu
D
D
Vinik
A I
AI
D000328:Adult; D017209:Apoptosis; D053938:DNA Fragmentation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003929:Diabetic Neuropathies / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D009447:Neuroblastoma / Q000473:pathology*; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor