Differential modulation of cell death proteins in human brain cells by tumor necrosis factor alpha and platelet activating factor

✍ Scribed by Lynn Pulliam; Mei Zhou; Marcia Stubblebine; Catherine M. Bitler

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 202 KB
• Volume: 54
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19981115)54:4<530::aid-jnr10>3.0.co;2-1

✦ Synopsis

Programmed cell death contributes to the morbidity and mortality of several neurological disorders including stroke, Alzheimer's disease and human immunodeficiency virus (HIV)-associated dementia. Patients with HIV dementia show evidence of programmed cell death in brain. In vitro data demonstrates several neurotoxic products of macrophage infection that cause neural cell death, including tumor necrosis factor ␣ (TNF␣) and platelet activating factor (PAF). We treated human brain aggregate cultures with these cytokines and determined their effect on the mRNA and protein levels for Bcl-2, Bcl x and Bax ␣. TNF␣ and PAF differentially regulate the Bcl-2 family of proteins at a post-transcriptional level. Following TNF␣ treatment, Bcl-2 protein is significantly decreased, and at least one additional Bax isomer emerges. Bcl xL protein is slightly increased after treatment with either cytokine. We demonstrated that overexpression of Bcl-2 in brain aggregate cultures protects cells from TNF␣-induced damage but has no effect on cell damage induced by PAF. We conclude that Bcl-2 and Bax ␣ proteins play significant roles in modulating neural cell death from TNF␣-but not from PAF-induced cell damage.