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Regulation of early response genes in pancreatic acinar cells: external calcium and nuclear calcium signalling aspects
Author(s) -
Fedirko N.,
Gerasimenko J. V.,
Tepikin A. V.,
Gerasimenko O. V.
Publication year - 2009
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2008.01935.x
Subject(s) - ryanodine receptor , extracellular , cholecystokinin , calcium , calcium signaling , stimulation , chemistry , receptor , microbiology and biotechnology , medicine , nuclear receptor , endocrinology , biology , biochemistry , gene , transcription factor , organic chemistry
Nuclear calcium signalling has been an important topic of investigation for many years and some aspects have been the subject of debate. Our data from isolated nuclei suggest that the nuclear pore complexes (NPCs) are open even after depletion of the Ca 2+ store in the nuclear envelope (NE). The NE contains ryanodine receptors (RyRs) and Ins(1,4,5)P 3 receptors [Ins(1,4,5)P 3 Rs], most likely on both sides of the NE and these can be activated separately and independently: the RyRs by either NAADP or cADPR, and the Ins(1,4,5)P 3 Rs by Ins(1,4,5)P 3 . We have also investigated the possible consequences of nuclear calcium signals: the role of Ca 2+ in the regulation of immediate early genes (IEG): c‐fos, c‐myc and c‐jun in pancreatic acinar cells. Stimulation with Ca 2+ ‐mobilizing agonists induced significant increases in levels of expression. Cholecystokinin (CCK) (10 n m ) evoked a substantial rise in the expression levels, highly dependent on external Ca 2+ : the IEG expression level was lowest in Ca 2+ ‐free solution, increased at the physiological level of 1 m m [Ca 2+ ] o and was maximal at 10 m m [Ca 2+ ] o , i.e.: 102 ± 22% and 163 ± 15% for c‐fos; c‐myc −73 ± 13% and 106 ± 24%; c‐jun −49 ± 8% and 59 ± 9% at 1 and 10 m m of extracellular Ca 2+ respectively. A low CCK concentration (10 p m ) induced a small increase in expression. We conclude that extracellular Ca 2+ together with nuclear Ca 2+ signals induced by CCK play important roles in the induction of IEG expression.