Trnascriptional regulation of neuronal nitric oxide synthase: role of creb and NF-kB-LIKE AP-2

초록

In the present study, we report that transcription of human nNOS exon 1f gene transcripts distributed predominantly in brain and gastrointestinal tract is controlled by dinucleotide repeated sequences (suppressive function of Z-DNA structure) and by two major transcriptional factors, cyclic-AMP response element binding protein (CREB) and nuclear factor kappa B-like activating protein-2 (NF-kB-like AP-2, NFkA). In various neuronal cells (SH-SY5Y, CATH.a, and PC12) and one muscle cells (NOR-10) transfected transiently with luciferase construct (pGL-2 basic vector) and containing CRE and/or NFkA binding sites modified by site-directed mutagenesis, the luciferase activity was decreased partially in the constructs containing the repeated sequences. Furthermore, in the cells containing the modified mutant forms, the complexicity of the major binding proteins decreased markedly. Based on the results, we suggest that transcription nNOS gene with exon 1f spliced form can be regulated by the proteins that bind to CRE and NFkA. This may be involved in the differential release of NO in the neuronal systems contained in brain and gastrointestinal tract