Contraction modulates the capacity for protein synthesis during growth of neonatal heart cells in culture.

Abstract

Neonatal ventricular myocytes that were incubated in a well-defined serum-free medium containing 50 mM KCl did not contract and maintained stable cell size, as assessed by the protein/DNA ratio. The present study utilized KCl-arrested cells to examine the effect of constant rates of synchronous contraction in normal [K+]o (4 mM) as a physiological stimulus for myocyte growth. Cell growth increased following the onset of contraction when measured over 3 days. The rate of protein synthesis was accelerated in parallel by contraction, but the rate of protein degradation remained similar to rates in noncontracting cells. The capacity for protein synthesis was estimated by total RNA content and was increased in contracting as compared with KCl-arrested cells. This increase was accompanied by faster rates of RNA synthesis as determined from the incorporation of [3H]uridine into RNA and the specific activity of the cellular UTP pool. The rate of RNA degradation was accelerated during contraction but the difference between the rates of RNA synthesis and degradation resulted in net RNA accumulation of 49% after 3 days. These data demonstrated that 1) contractile activity stimulated myocyte growth through an increased capacity for protein synthesis and 2) the increased capacity for protein synthesis involved acceleration of the rate of RNA synthesis. Since enhancement of protein synthetic capacity is a common feature of myocyte hypertrophy in vivo and in vitro, this model can be used to examine the regulation of ribosome synthesis during hypertrophic growth.

Heart regeneration in adult MRL mice

“…It seems then, that the MRL mouse heart recovers right ventricular function within 3 months of injury. It is well known that in myocardial tissue culture, the lack of continued myocardial loading with stimulation leads to a rapid loss of the normal cytoarchitecture, function (49), and protein synthesis (50). Therefore, because the MRL myocardium in the area of the BrdUrd uptake shows normal sarcomeres, it is very unlikely that these cardiomyocytes are not functional.…”

Left ventricular insulin-like growth factor I increases in early renal hypertension.

“…Increased coronary perfusion pressure stimulates protein synthesis in isolated perfused hearts 27 as well as external load in the absence of other trophic factors in isolated feline cardiomyocytes 28 and the mere presence of contractions in cultured neonatal cardiomyocytes. 29 However, coronary perfusion pressure and flow as well as contractions per se will also affect both ventricles to the same extent and are thus less probable as stimuli to IGF-I synthesis. The increased left ventricular work load would be a more likely candidate to explain the raised IGF-I levels in the left ventricle, and this assumption is also strengthened by the present observation that IGF-I protein seems to be more abundant in the inner layers of the myocardium ( Figure 5E).…”

Beneficial effect of taurine depletion on osmotic sodium and calcium loading during chemical hypoxia

“…Rat neonatal cardiomyocytes were isolated according to the method of McDermott and Morgan (12). The cells were suspended in minimal essential medium containing 10% newborn calfserum and 0.1 mM 5Ј-bromo-2Ј-deoxyuridine and plated on either glass coverslips or glass petri dishes precoated with 0.1% gelatin.…”