Alterations of enzymatic activities during muscle differentiation in vitro.
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Biomedical subjects
A Shainberg
Publications and source records attributed to A Shainberg.
Control of myogenesis in vitro by Ca 2 + concentration in nutritional medium.
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SEM observations on the effect of anthracycline drugs on cultured newborn rat cardiomyocytes.
The effect of two anthracyclines-doxorubicin hydrochloride (adriamycin) and 4'-epidoxorubicin (epirubicin) and an anthracenedione (novantrone) on the contractibility and surface ultrastructure of newborn rat cardiomyocytes cultured for five days was examined. While the beating rate of the cells was affected only by the anthracyclines, an alteration of the sarcolemma, disruption of the slender processes and swelling of the nuclei and/or the cells was observed following incubation with each of the three drugs for two hours. However, the damage induced by adriamycin was more pronounced than that induced by the other two drugs, when doses extrapolated from those accepted as therapeutic were compared.
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Thyroxine induces transition of red towards white muscle in cultured heart cells.
Thyroid hormones (TH) have previously been shown to alter the force and velocity of cardiac muscle contractions. To investigate the mechanism responsible for these alterations, excess amounts of thyroxine (T4, 1 microM) were applied on rat heart cells grown in cell culture. We found the following biochemical alterations: a) 40% decrease in the myoglobin content within 2 days; b) 25% increase in the rate of Ca-uptake into sacroplasmic reticulum (SR) in myocytes following chemical skinning; and c) a two-fold increase in Na-K-ATPase activity measured by 86Rb-uptake. These changes support our hypothesis that TH induce the transition of slow-twitch ("red") muscles towards the fast-twitch ("white") muscle type. This may explain the changes in contractile activity known to occur under TH influence.
Animals↗
Regulation of beta-adrenoceptors by thyroid hormone and amiodarone in rat myocardiac cells in culture.
Hyperthyroidism is associated with elevation of heart cells sensitivity to catecholamines. We demonstrated that T3(10(-8) M) increased (30%) the number of beta-adrenoceptors in intact heart cells grown in vitro within 48 hr, without changing the affinity of the ligand [3H]CGP-12177. The increase in beta-adrenoceptors in T3-treated myocytes was not associated with an increase in receptor-mediated cAMP production. Amiodarone, an antiarrhythmic drug, reduces the sensitivity of the heart to catecholamines. To investigate this effect, we analysed the influence of amiodarone on the level of beta-adrenergic receptors. Ninety minute preincubation with amiodarone (5 x 10(-5) M) decreased the number of beta-adrenoceptors (35-50%) in intact heart cells and in heart membranes, without affecting the dissociation constants (Kd). Amiodarone inhibited isoproterenol induced cAMP production. These results indicate that the mechanism of action of amiodarone on the heart seems to be a non-competitive inhibition of catecholamine receptors.
Adrenergic beta-Antagonists↗
Selective neurotoxicity induced by the ionophore lasalocid in rat dissociated cerebral cultures, involvement of the NMDA receptor/channel.
An in vitro model of dissociated cerebral cultures, prepared from prenatal 15-16-days rat fetuses, was used to further characterize the neurotoxic effects caused by the antibiotic ionophore lasalocid-X-537A. The damage caused by lasalocid (1-2 microM, 2-4 hr) included swelling of perikarya, followed by cytolysis of most neurons present in the cultures. The neuronal damage was dose-dependent, noticeable at concentrations above 0.5 microM, and was more pronounced in established cultures (14 days in vitro-DIV) than in younger ones (7 DIV). Unlike neurons, no damage was observed in glia and other non-neuronal cells present in the cultures by exposure to 2 microM lasalocid. Moreover, the drug was not toxic for cultures of rat astrocytes and C6 glioma cells. Another calcium ionophore A-23187 (calcimycin, 1 microM), destroyed both neuronal and non-neuronal cells within 1 hr. Ca2+ influx was increased by 140% in cultures exposed to lasalocid (1.5 microM). The lasalocid neurotoxic effects were neither inhibited by 10 microM nimodipine (a calcium channel antagonist) nor by 10 microM 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)(a non-N-methyl-D-aspartic acid (NMDA) receptor antagonist), but were exclusively blocked by 10 microM MK-801 (a non-competitive NMDA receptor/channel antagonist). The neurotoxicity induced by lasalocid was further confirmed by measurements of lactate dehydrogenase (LDH) released into the media. Lasalocid (1.5 microM) induced the release of both LDH and arachidonic acid (AA) (by 8 and 4 fold of control values, respectively), and this was blocked by MK-801 but not by CNQX. These results are in according with the observations that activation of calcium influx through the NMDA receptor leads to activation of phospholipase A2 (PLA2) and release of AA. In contrast, MK-801 did not block the release of either LDH or AA mediated by the calcium ionophore A-23187 (1 microM) in these cultures. [3H]-MK-801 binding to washed rat cortical membranes, a measure of direct interaction with the NMDA receptor/channel complex, was not affected by lasalocid either alone or in the presence of glutamate and glycine. [3H]-D-aspartate release, a measure of excitatory amino acid (EAA) secretion mediated by NMDA receptor activation, was increased by lasalocid and could be blocked by MK-801. These observations suggest that lasalocid induces selective neurotoxicity, which involves the NMDA receptor/channel complex, possibly indirectly, resulted in elevated intracellular Ca2+ levels and the subsequent glutamate or aspartate release.
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