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Endothelin increases expression of exon III‐ and exon IV‐containing brain‐derived neurotrophic factor transcripts in cultured astrocytes and rat brain
Author(s) -
Koyama Yutaka,
Tsujikawa Kimiko,
Matsuda Toshio,
Baba Akemichi
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20512
Subject(s) - exon , brain derived neurotrophic factor , neurotrophic factors , ciliary neurotrophic factor , neuroscience , endothelin 1 , biology , microbiology and biotechnology , endocrinology , medicine , genetics , gene , receptor
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 IV‐containing 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 2+ ‐chelation, W‐7 (a calmodulin inhibitor), and KN93 (a Ca 2+ /calmodulin kinase inhibitor) inhibited the increases in exon IV BDNF mRNA and CCAAT enhancer‐binding protein β (C/EBPβ) 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 2+ 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/EBPβ‐mediated mechanisms, respectively. © 2005 Wiley‐Liss, Inc.