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Pathways regulating Na+/Ca2+ exchanger expression in the heart.

Donald R Menick·Lin Xu·Christina Kappler·Wenjing Jiang·Patrick Withers·Neal Shepherd·Simon J Conway·Joachim G Müller
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Abstract

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 alpha-adrenergic-induced NCX1 upregulation by 30%. Overexpression of DN-JNK lowered basal NCX1 expression. Overexpression of activated MKK-3 was sufficient for alpha-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 alpha-adrenergic-stimulated NCX1 upregulation, and (3) p38 activation alone is sufficient for NCX1 upregulation.

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5' Untranslated RegionsAnimalsBase SequenceCatsDisease Models, AnimalExonsGene Expression RegulationHeartIntegrinsJNK Mitogen-Activated Protein KinasesMAP Kinase Signaling SystemMiceMice, TransgenicMitogen-Activated Protein KinasesMuscle CellsPromoter Regions, GeneticRNA SplicingSodium-Calcium ExchangerJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.Review

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Donald R Menick, Lin Xu, Christina Kappler, Wenjing Jiang, Patrick Withers, Neal Shepherd, Simon J Conway, Joachim G Müller. 2002. Pathways regulating Na+/Ca2+ exchanger expression in the heart.. https://doi.org/10.1111/j.1749-6632.2002.tb04746.x

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