Alpha 1-adrenergic stimulation of rat myocardial cells increases protein synthesis

Abstract

The effects of adrenergic stimulation on the rates of protein synthesis, degradation, and accumulation were examined in primary cultures of neonatal rat heart cells. Treatment of myocardial cells with norepinephrine increased total cellular protein content and the rate of incorporation of radiolabeled tyrosine into trichloroacetic acid insoluble protein. alpha 1-Adrenergic, but not alpha 2- or beta-adrenergic blockade, inhibited these norepinephrine induced increases. The rate of protein synthesis estimated from the kinetics of equilibrium labeling and from combined equilibrium and pulse labeling was increased by norepinephrine stimulation, whereas protein degradation estimated by release of previously incorporated radiolabeled tyrosine or in pulse-chase experiments was unaffected. To determine whether alpha 1-adrenergic stimulation produced similar effects on the turnover of myofibrillar proteins, rates of synthesis and degradation were estimated for a myofibrillar-enriched protein fraction and for myosin heavy chain and actin. Norepinephrine treatment produced increases in the synthesis of myofibrillar protein without significantly altering degradation rates. These experiments suggest that alpha 1-adrenergic stimulation increases myocardial cell protein content by accelerating protein synthesis.

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

“…MLC-2 is one of the contractile proteins of the cardiac myosin and has been reported to be a useful marker for cardiac hypertrophy (Meidell et al, 1986;Lee et al, 1988;Sen et al, 1988;Henderson et al, 1989;Doud et al, 1995). For example, spontaneous cardiac hypertrophy in rats is accompanied by increases in the amount of MLC-2 mRNA (Lee et al, 1988), and -adrenergic stimulation of neonatal rat myocardial cells produces several features of myocardial hypertrophy, including a several-fold increase in the volume of the MLC-2 gene (Kummar et al, 1986).…”

“…The amounts ofmyosin heavy chain (Waspe et al,1990), -actin (Bishopric et al, 1987), and myosin light chain-2 (MLC-2; Kummar et al, 1986) increase 3, 4, and 4 times, respectively. Among these contractile proteins, MLC-2, one of the cardiac myosin molecules (Emerson and Bernstein, 1987), has been used extensively as a marker protein for myocardial hypertrophy (Meidell et al, 1986;Lee et al, 1988;Sen et al, 1988;Henderson et al, 1989;Doud et al, 1995). Phosphorylation of MLC-2 modulates the contractile activity of cardiac cells (Silver et al, 1986;Stull et al, 1985;Morano, 1999).…”

Direct Association of the Gap Junction Protein Connexin-43 with ZO-1 in Cardiac Myocytes

“…Cell Culture-Rat neonatal cardiac myocytes were prepared as described previously (17). Briefly, the hearts were isolated from 1-day-old HLA-Wistar rats.…”

Cardiac α1‐adrenoceptor densities in different mammalian species

“…It has been suggested that the a,-adrenoceptor-mediated response may become important under certain pathological conditions including ischaemia (Penny et al, 1985), abnormal thyroid function (Williams et al, 1977), dysrhythmogenesis (Sheridan et al, 1980) and hypertension (Yamada et al, 1984). ajAdrenoceptors may also be involved in other processes such as protein synthesis (Meidell et al, 1986) and cardiac hypertrophy (Simpson, 1990). Radioligand binding studies have been performed on several myocardial preparations (Williams & Lefkowitz, 1978;Rugevics & Schumann, 1987;Bevilacqua et al, 1987;Steinkraus et al, 1989;Shen et al, 1989) revealing intra-and interspecies differences in the density of cladrenoceptors which might partially be due to different experimental conditions.…”