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

Donald R. Menick, Lin Xu, Christiana Kappler, Wenjing Jiang, Patrick R. Withers, Neal Shepherd, Simon J. Conway, Joachim G. Müller

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The Na+/Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)237-247
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume976
StatePublished - Jan 1 2002

    Fingerprint

Keywords

  • Gene expression
  • Hypertrophy
  • Integrins
  • MAP kinases
  • Regulation
  • Signal transduction
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Menick, D. R., Xu, L., Kappler, C., Jiang, W., Withers, P. R., Shepherd, N., Conway, S. J., & Müller, J. G. (2002). Pathways regulating Na+/Ca2+ exchanger expression in the heart. Annals of the New York Academy of Sciences, 976, 237-247.