Journal
NEUROREPORT
Volume 19, Issue 3, Pages 265-269Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WNR.0b013e3282f4cb50
Keywords
autoimmunity; autophagy; diabetic neuropathy; Fas (CD95); type 2 diabetes
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Funding
- NCRR NIH HHS [RR024986, M01-RR-00042] Funding Source: Medline
- PHS HHS [R01-052387, R01-056997] Funding Source: Medline
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We reported previously that sera from patients with type 2 diabetes and neuropathy induce autophagy in human neuroblastoma (SH-SY5Y) cells. Here we report that enriched immunoglobulin fractions from a subpopulation of these patients induce autophagy and colocalization with Fas-activated death domain (FADD), a component of the Fas-activated death domain receptor signaling pathway. These effects were replicated by treatment of SY5Y cells with Fas ligand, tumor necrosis factor alpha and an agonist anti-Fas antibody. Preincubation of these sera with a soluble Fas receptor chimera (extracellular domain) markedly decreased the stimulation of autophagy. The results suggest that sera from subset of individuals with type 2 diabetes and neuropathy contain autoantibodies that activate the Fas cascade.
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