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Pathways Regulating Na + /Ca 2+ Exchanger Expression in the Heart
Author(s) -
MENICK DONALD R.,
XU LIN,
KAPPLER CHRISTIANA,
JIANG WENJING,
WITHERS PATRICK R.,
SHEPHERD NEAL,
CONWAY SIMON J.,
MÜLLER JOACHIM G.
Publication year - 2002
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 - 10.1111/j.1749-6632.2002.tb04746.x
Subject(s) - downregulation and upregulation , mapk/erk pathway , gene expression , p38 mitogen activated protein kinases , microbiology and biotechnology , chemistry , regulation of gene expression , kinase , biology , gene , biochemistry
A bstract : The Na + /Ca 2+ exchanger (NCX1) is regulated at the transcriptional level in cardiac hypertrophy, ischemia, and failure. Following pressure overload, activation of MAPKs coincides with the kinetics of NCX1 gene upregulation in adult cardiocytes. Using adenoviral gene delivery, we begin to identify the molecular pathways responsible for upregulation of the exchanger gene. Inhibition of ERK with the MEK inhibitor UO126, the ERK protein phosphatase MKP‐3, inhibited ERK activation, but only inhibited α‐adrenergic‐induced NCX1 upregulation by 30%. Overexpression of DN‐JNK lowered basal NCX1 expression. Overexpression of activated MKK‐3 was sufficient for α‐adrenergic‐stimulated upregulation of the reporter gene. Together, this data indicates that (1) JNK mediates basal cardiac expression of the NCX1 gene, (2) ERK and p38 play a role in α‐adrenergic‐stimulated NCX1 upregulation, and (3) p38 activation alone is sufficient for NCX1 upregulation.