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Rapid induction and Ca 2+ influx‐mediated suppression of vitamin D3 up‐regulated protein 1 (VDUP1) mRNA in cerebellar granule neurons undergoing apoptosis
Author(s) -
Saitoh Tatsuya,
Tanaka Shuuitsu,
Koike Tatsuro
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00505.x
Subject(s) - apoptosis , messenger rna , neuroprotection , kinase , microbiology and biotechnology , biology , protein kinase a , p38 mitogen activated protein kinases , gene expression , phosphorylation , gene , biochemistry , neuroscience
Cerebellar granule neurons (CGNs) grown under depolarizing conditions with high K + (HK; 30 m m ) undergo apoptosis following replacement of HK by physiological K + (5.4 m m ). Differential display analysis identified eight genes up‐regulated in this paradigm of apoptosis. Vitamin D3 up‐regulated protein 1 ( VDUP1 ) mRNA was markedly up‐regulated as early as 2 h following HK withdrawal. VDUP1 mRNA was up‐regulated in other paradigms of neuronal apoptosis as well both in vitro and in vivo . HK effectively suppressed the up‐regulation of VDUP1 mRNA in CGNs undergoing apoptosis via Ca 2+ influx through voltage‐dependent L ‐type Ca 2+ channels, which did not require de novo protein synthesis. The up‐regulation occurred in parallel with that of the c‐ jun transcript and c‐jun protein phosphorylation. Moreover, SB203580, p38 mitogen‐activated protein kinase inhibitor, suppressed up‐regulation of both c‐ jun and VDUP1 mRNAs, and c‐jun phosphorylation in CGNs undergoing apoptosis. IGF‐1, one of the neuroprotective agents for CGNs, also inhibited VDUP1 mRNA up‐regulation through a phosphoinositide 3 kinase‐dependent pathway. These results suggest that the VDUP1 gene is a novel member of early response genes in neuronal apoptosis whose expression is directly regulated by Ca 2+ influx and coordinately regulated with the transcription factor c‐ jun in CGNs.