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Regulation of Ncx1 Gene Expression in the Normal and Hypertrophic Heart
Author(s) -
MENICK DONALD R.,
RENAUD LUDIVINE,
BUCHHOLZ AVERY,
MÜLLER JOACHIM G.,
ZHOU HONGMING,
KAPPLER CHRISTIANA S.,
KUBALAK STEVEN W.,
CONWAY SIMON J.,
XU LIN
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.058
Subject(s) - gene , gene expression , medicine , biology , genetics
The Na + /Ca 2+ exchanger (NCX1) is crucial in the regulation of [Ca 2+ ] i in the cardiac myocyte. The exchanger is upregulated in cardiac hypertrophy, ischemia, and failure. This upregulation can have an effect on Ca 2+ transients and possibly contribute to diastolic dysfunction and an increased risk of arrhythmias. Studies from both in vivo and in vitro model systems have provided an initial skeleton of the potential signaling pathways that regulate the exchanger during development, growth, and hypertrophy. The Ncx1 gene is upregulated in response to α‐adrenergic stimulation. We have shown that this is via p38α activation of transcription factors binding to the Ncx1 promotor at the –80 CArG element. Interestingly, most of the elements, including the CArG element, which we have demonstrated to be important for regulation of Ncx1 expression are in the proximal 184 bp of the promotor. Using a transgenic mouse, we have shown that the proximal 184 bp is sufficient for expression of reporter genes in adult cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in development but not for upregulation in response to pressure overload.