Abstract

Recently, a novel amyloid precursor protein beta-secretase (designated BACE) was identified. Because activated microglia and astrocytes play a role in amyloidogenesis in Alzheimer's disease, the constitutive and glial cytokine/growth factor-regulated expression of BACE was studied in human neural cell lines. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, BACE mRNA expression was identified in various human neural and non-neural cell lines. By northern blot analysis, the expression of BACE mRNA composed of five distinct transcripts (>8.0, 7.0, 6.0, 4.4 and 2.6 kb) was elevated markedly in NTera2 teratocarcinoma cells following retinoic acid-induced neuronal differentiation. But the levels of three major BACE mRNA species (7.0, 6.0 and 4.4 kb) were not significantly altered in NTera2-derived neurons, SK-N-SH neuroblastoma or U-373MG astrocytoma following exposure to tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, interferon-gamma, transforming growth factor-beta1, epidermal growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor, dibutyryl cyclic adenosine monophosphate or phorbol 12-myristate 13-acetate. These results indicate that BACE mRNA is expressed constitutively in human neural cells and its expression is upregulated during neuronal differentiation, but it is unlikely to be regulated by activated glia-derived cytokines and growth factors.