36 research outputs found
Cl Anion-Dependent Mg-ATPase
We studied, in the rat brain, the synaptosomal and microsomal membrane fractions of Cl− ion-activated, Mg2+-dependent ATPase, satisfying the necessary kinetic peculiarities of transport ATPases, by a novel method of kinetic analysis of the multisite enzyme systems: (1) the [Mg-ATP] complex constitutes the substrate of the enzymic reaction; (2) the V = f(Cl−) dependence-reflecting curve is bell-shaped; (3) substrate dependence, V = f(S), curves at a constant concentration of free ligands (Mgf, ATPf, Cl−); (4) as known from the literature, in the process of reaction a phosphorylated intermediate is formed (Gerencser, Crit Rev Biochem Mol Biol 31:303–337, 1996). We report on the Cl-ATPase molecular mechanism and its place in the “P-type ATPase” classification
Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
BACKGROUND: Despite years of interest in the anti-cancerous effects of cardiac glycosides (CGs), and numerous studies in vitro and in animals, it has not yet been possible to utilize this potential clinically. Reports have demonstrated promising in vitro effects on different targets as well as a possible therapeutic index/selectivity in vitro and in experimental animals. Recently, however, general inhibition of protein synthesis was suggested as the main mechanism of the anti-cancerous effects of CGs. In addition, evidence of species differences of a magnitude sufficient to explain the results of many studies called for reconsideration of earlier results. PRINCIPAL FINDINGS: In this report we identified primary B-precursor and T-ALL cells as being particularly susceptible to the cytotoxic effects of CGs. Digitoxin appeared most potent and IC(50) values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC(50) was demonstrated in colorectal tumour cell lines moderately resistant to the cytotoxic effects of digoxin and digitoxin, but not in highly sensitive leukaemia cell lines. CONCLUSION: It is suggested that further investigation regarding CGs may be focused on diagnoses like T- and B-precursor ALL