Protection of neuronal cell death against diabetes-induced apoptosis by Fas blocker ZB4

• Published in: Journal of international medical research 2014-08, Vol.42 (4), p.949-957
• Main Authors: Rouq, Fawzia Al, Hammad, Durdana, Meo, Sultan Ayoub
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antibodies, Monoclonal - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Diabetes Complications - pathology; Diabetes Mellitus - pathology; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - prevention & control; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fas Ligand Protein - blood; fas Receptor - antagonists & inhibitors; fas Receptor - blood; fas Receptor - metabolism; Female; Humans; Male; Medical sciences; Mice; Middle Aged; Neurons - physiology; Pharmacology. Drug treatments; Young Adult
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/0300060513510656

Objective To determine the role of apoptosis inhibition in the prevention of diabetic neuropathy using the antiFas cell surface death receptor (Fas) antagonistic monoclonal antibody ZB4. Methods This prospective study enrolled patients with type 2 diabetes with and without neuropathy and a group of healthy controls. The serum concentrations of Fas and Fas ligand (FasL) were measured in all study participants using an enzyme-linked immunosorbent assay. The ability of serum from study participants to induce apoptosis was evaluated in a human neuronal cell line using flow cytometry. Results A total of 28 healthy subjects and 57 patients with diabetes were enrolled in the study. Serum Fas concentrations were significantly increased in diabetes patients with and without neuropathy compared with the controls. Cells treated with the serum from diabetes patients with neuropathy had significantly higher rates of early apoptosis compared with cells treated with control serum. Monoclonal antibody ZB4 was able to block serum-induced apoptosis. Conclusions Serum-induced apoptosis of a human neuronal cell line appeared to be mediated via Fas, which suggests that targeting and inhibiting Fas might offer a therapeutic target for diabetic neuropathy.