Role of protein kinase C-ε in hypertrophy of cultured neonatal rat ventricular myocytes

James B. Strait, Jody L. Martin, Allison Bayer, Ruben Mestril, Diane M. Eble, Allen M. Samarel

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Using adenovirus (Adv)-mediated overexpression of constitutively active (ca) and dominant-negative (dn) mutants, we examined whether protein kinase C (PKC)-ε, the major novel PKC isoenzyme expressed in the adult heart, was necessary and/or sufficient to induce specific aspects of the hypertrophic phenotype in low-density, neonatal rat ventricular myocytes (NRVM) in serum-free culture. Adv-caPKC-ε did not increase cell surface area or the total protein-to-DNA ratio. However, cell shape was markedly affected, as evidenced by a 67% increase in the cell length-to-width ratio and a 17% increase in the perimeter-to-area ratio. Adv-caPKC-ε also increased atrial natriuretic factor (ANF) and β-myosin heavy chain (MHC) mRNA levels 2.5 ± 0.3- and 2.1 ± 0.2-fold, respectively, compared with NRVM infected with an empty, parent vector (P < 0.05 for both). Conversely, Adv-dnPKC-ε did not block endothelin-induced increases in cell surface area, the total protein-to-DNA ratio, or upregulation of β-MHC and ANF gene expression. However, the dominant-negative inhibitor markedly suppressed endothelin-induced extracellular signal-regulated kinase (ERK) 1/2 activation. Taken together, these results indicate that caPKC-ε overexpression alters cell geometry, producing cellular elongation and remodeling without a significant, overall increase in cell surface area or total protein accumulation. Furthermore, PKC-ε activation and downstream signaling via the ERK cascade may not be necessary for cell growth, protein accumulation, and gene expression changes induced by endothelin.

Original languageEnglish (US)
Pages (from-to)H756-H766
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
DOIs
StatePublished - Feb 2001
Externally publishedYes

Keywords

  • Adenovirus
  • Endothelin-1
  • Extracellular signal-regulated kinase
  • Heart
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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