PMID- 18303564 OWN - NLM STAT- MEDLINE DCOM- 20080409 LR - 20171116 IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 19 IP - 3 DP - 2008 Feb 12 TI - Type 2 diabetes with neuropathy: autoantibody stimulation of autophagy via Fas. PG - 265-9 LID - 10.1097/WNR.0b013e3282f4cb50 [doi] AB - 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. FAU - Towns, Roberto AU - Towns R AD - Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA. FAU - Guo, Chunfang AU - Guo C FAU - Shangguan, Yu AU - Shangguan Y FAU - Hong, Shuangsong AU - Hong S FAU - Wiley, John W AU - Wiley JW LA - eng GR - M01-RR-00042/RR/NCRR NIH HHS/United States GR - R01-052387/PHS HHS/United States GR - R01-056997/PHS HHS/United States GR - RR024986/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Autoantibodies) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin M) RN - 0 (fas Receptor) SB - IM MH - Adult MH - Autoantibodies/*immunology MH - Autophagy/*genetics/*physiology MH - Blotting, Western MH - Cell Line, Tumor MH - Diabetes Mellitus, Type 2/*immunology/*pathology MH - Diabetic Neuropathies/*immunology/*pathology MH - Female MH - Fluorescent Antibody Technique MH - Humans MH - Image Processing, Computer-Assisted MH - Immunoglobulin G/biosynthesis/genetics MH - Immunoglobulin M/biosynthesis/genetics MH - Male MH - Neuroblastoma/pathology MH - fas Receptor/genetics/*physiology EDAT- 2008/02/28 09:00 MHDA- 2008/04/10 09:00 CRDT- 2008/02/28 09:00 PHST- 2008/02/28 09:00 [pubmed] PHST- 2008/04/10 09:00 [medline] PHST- 2008/02/28 09:00 [entrez] AID - 00001756-200802120-00002 [pii] AID - 10.1097/WNR.0b013e3282f4cb50 [doi] PST - ppublish SO - Neuroreport. 2008 Feb 12;19(3):265-9. doi: 10.1097/WNR.0b013e3282f4cb50.