Differential regulation of Na+/H+ antiporter gene expression in vascular smooth muscle cells by hypertrophic and hyperplastic stimuli

Rao Gadiparthi, C. Sardet, J. Pouyssegur, B. C. Berk

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Abstract

The Na+/H+ antiporter is a ubiquitous transmembrane protein that plays a vital role in cell growth via regulation of intracellular Na+ and H+. In vascular smooth muscle cells (VSMC), vasoconstrictors and mitogens rapidly activate the antiporter, suggesting that both sould have growth promoting effects. Indeed, angiotensin II increases VSMC protein and volume (hypertrophy), but does not increase cell number (hyperplasia). In the present work we investigated whether alterations in the steady state levels of Na+/H+ antiporter mRNA might differentiate these VSMC growth responses. Differences in function of the Na+/H+ antiporter appeared likely because exposure of growth-arrested VSMC for 24 h to 100 nM angiotensin II decreased intracellular pH from 7.08 to 6.99, while exposure to 10% calf serum caused an increase to 7.18. Simultaneous measurement of Na+/H+ antiporter mRNA levels, using the human c28 cDNA, revealed a 25-fold increase in response to serum (as well as to platelet-derived and fibroblast growth factors), but no change in response to angiotensin II. All agonists increased mRNA levels of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase approximately 3-fold. The increase in Na+/H+ antiporter mRNA induced by serum was first apparent within 2 h and peaked 24 h after treatment. These results demonstrate that expression of Na+/H+ antiporter mRNA in VSMC is dependent on growth state: hyperplastic agonists (serum, platelet-derived and fibroblast growth factor) increase the steady state levels of Na+/H+ antiporter mRNA while a hypertrophic agonist (angiotensin II) does not.

Original languageEnglish (US)
Pages (from-to)19393-19396
Number of pages4
JournalJournal of Biological Chemistry
Volume265
Issue number32
StatePublished - Dec 17 1990

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Sodium-Hydrogen Antiporter
Vascular Smooth Muscle
Gene expression
Smooth Muscle Myocytes
Muscle
Cells
Gene Expression
Angiotensin II
Messenger RNA
Growth
Fibroblast Growth Factors
Platelet-Derived Growth Factor
Cell growth
Serum
Antiporters
Glyceraldehyde-3-Phosphate Dehydrogenases
Muscle Proteins
Vasoconstrictor Agents
Cell Size
Mitogens

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Differential regulation of Na+/H+ antiporter gene expression in vascular smooth muscle cells by hypertrophic and hyperplastic stimuli. / Gadiparthi, Rao; Sardet, C.; Pouyssegur, J.; Berk, B. C.

In: Journal of Biological Chemistry, Vol. 265, No. 32, 17.12.1990, p. 19393-19396.

Research output: Contribution to journalArticle

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