Volume 2, Issue 1, 2008

A Proposed Mechanism for OTK18 Regulation of TNF-α in Response to Neurotoxic Insult

Stephanie L. Larson, Christine E. Gilling, Kimberly A. Carlson

Abstract

OTK18, a transcriptional suppressor with putative anti-retroviral properties, is found at the highest levels in severe human immunodeficiency virus type-1 encephalitic brains. The role of OTK18 up-regulation in neuronal survival and corresponding responses of tumor necrosis factor-alpha (TNF-α) and neurotrophin 3 (NT3) was examined. Rat pheochromocytoma cells were transfected with either pEGFP-OTK18 or empty vector, glutamate treated, and cell viability assessed. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay analyses showed significant up-regulation of TNF-α message and protein in pEGFP-OTK18 transfected cells compared to controls. These results suggest a potential role for OTK18 in regulating TNF-α and subsequent neuronal demise. Full Article