Endothelin increases expression of exon III- and exon IV-containing brain-derived neurotrophic factor transcripts in cultured astrocytes and rat brain

✍ Scribed by Yutaka Koyama; Kimiko Tsujikawa; Toshio Matsuda; Akemichi Baba

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 441 KB
• Volume: 80
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20512

✦ Synopsis

The effects of endothelins (ETs) on brain-derived neurotrophic factor (BDNF) production in astrocytes were investigated. ET-1 (100 nM) increased the mRNA level and extracellular release of BDNF in cultured astrocytes. RT-PCR analyses using primer pairs that amplified exon-specific BDNF transcripts revealed that exon III-and exon IVcontaining BDNF transcripts existed in cultured astrocytes, whereas exon I-and exon II-containing BDNF transcripts did not. ET-1 and Ala 1,3,11,15 -ET-1, an ET B receptor agonist, increased the expressions of the exon III and exon IV transcripts in cultured astrocytes. Intracerebroventricular administration of 500 pmol/day of Ala 1,3,11,15 -ET-1 increased exon III and exon IV BDNF transcripts in the rat striatum. In cultured astrocytes, Ca 2þ -chelation, W-7 (a calmodulin inhibitor), and KN93 (a Ca 2þ /calmodulin kinase inhibitor) inhibited the increases in exon IV BDNF mRNA and CCAAT enhancer-binding protein b (C/EBPb) levels induced by ET-1. The ET-induced increases in exon III BDNF mRNA expression and phosphorylation of cAMP response element binding protein (CREB) were reduced by Ca 2þ chelation, W-7, KN93, PD98059 (a MEK inhibitor), and wortmannin (a phosphatidylinositol 3-kinase inhibitor). These results suggest that ETs stimulate the expressions of exon III and exon IV BDNF transcripts in astrocytes through CREB and C/EBPb-mediated mechanisms, respectively.