Increased expression of eukaryotic initiation factor 4E during growth of neonatal rat cardiocytes in vitro.

Eukaryotic initiation factor 4E (eIF-4E) is rate limiting for translational initiation. The purpose of this study was to determine whether eIF-4E levels are increased during cardiocyte growth produced by increased load in the form of electrically stimulated contraction. Neonatal rat cardiocytes were cultured on a matrix of aligned type I collagen. The cardiocytes aligned in parallel to the direction of the collagen fibrils and exhibited an elongated, rod-shaped morphology. Cardiocytes were electrically stimulated to contract at 3 Hz (alternating polarity, 5-ms pulse width). Nonstimulated cardiocytes were quiescent and used as controls. Electrically stimulated contraction produced hypertrophic growth as determined by the following criteria: 1) increased protein content, 2) increased RNA content, 3) accelerated rate of protein synthesis, and 4) threefold increase in promoter activity of the atrial natriuretic factor gene. Cardiocyte growth was associated with an increase in eIF-4E mRNA levels that reached 48 +/- 9% after 2 days of electrically stimulated contraction. eIF-4E protein levels were increased by more than twofold over the same time period. We conclude that an adaptive increase in eIF-4E is an important mechanism for maintaining translational efficiency during cardiocyte growth.