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Biomedical subjects

N Siliprandi

Publications and source records attributed to N Siliprandi.

At least 73 records · Page 4Linked to original sources

Restoration of membrane potential in mitochondria deenergized with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP).

The membrane potential (delta psi) of rat liver mitochondria dropped upon addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) but was gradually and fully restored to the original value by the subsequent addition of dithioerythritol. Concomitantly, Ca2+ released from mitochondria was reaccumulated and the oxidative phosphorylation process completely recoupled. Neither of these effects has been observed with dinitro-o-cresol or 2,4-dinitrophenol, uncouplers which, unlike FCCP, do not react with thiols. Delta psi abolished by FCCP was also restored, though incompletely, by albumin; a prompt and complete restoration was however achieved upon subsequent addition of dithioerythritol. Dithioerythritol also completely and rapidly restored the delta psi decreased by addition of diazene dicarboxylic acid bisdimethylamide (diamide).

Animals↗

Effect of carnitine on serum HDL-cholesterol: report of two cases.

In two otherwise normal male subjects selected for normal serum cholesterol and triglycerides but low serum high-density lipoprotein (HDL) levels, oral administration of 1 g per day of L-carnitine over a period of 10-15 weeks caused a substantial increase in high-density lipoprotein levels, as well as a decrease in serum triglycerides. The ratio of HDL-cholesterol to total cholesterol increased, but this change was not due to an obligatory lowering of total cholesterol. Possible mechanisms of the carnitine effect are discussed. Since elevated high-density lipoprotein levels significantly reduce the risk of arteriosclerotic cardiovascular disease, this action of carnitine deserves further study.

Carnitine↗

Parallel efflux of Ca2+ and Pi in energized rat liver mitochondria.

Addition of Ruthenium Red to energized rat liver mitochondria that have previously accumulated Ca2+ and phosphate from the external medium induces a parallel efflux of both these ions. Mersalyl or dithioerythritol, which decrease Ruthenium Red-insensitive Ca2+ efflux, also decrease phosphate efflux to the same extent. Conversely diazenedicarboxylic acid bis(NN-dimethylamide) (DDBA), which increases the Ruthenium Red-induced Ca2+ efflux concurrently increases phosphate release. Dithioerythritol and DDBA, reducing and oxidizing agents of thiol groups respectively, modify Ca2+ and Pi efflux without penetrating the mitochondrial inner membrane. Under all the adopted conditions the membrane potential is preserved. The release of resting respiration and the parallel efflux of Mg2+ and adenine nucleotides, events closely correlated to Ca2+ cycling, are equally prevented either by mersalyl, which inhibits phosphate transport, or dithioerythritol; DDBA has the opposite effect. These findings and the observation that suggest that Ca2+ and phosphate transport in energized liver mitochondria are closely related and dependent on the redox state of membrane-bound thiol groups.

Adenine Nucleotides↗

Correlated effluxes of adenine nucleotides, Mg2+ and Ca2+ induced in rat-liver mitochondria by external Ca2+ and phosphate.

The presence of inorganic phosphate and Ca2+ in the external medium induces a closely parallel efflux of both endogenous adenine nucleotides and Mg2+ from rat liver mitochondria. These effluxes are (a) pH-dependent and inhibited by uncouplers, respiration inhibitors and external Mg2+; (b) completely prevented by bongkrekate, but stimulated by atractylate. ATP, ADP or AMP each inhibit the release of Mg2+ promoted by Ca2+ and phosphate; however, in the presence of oligomycin and P1,P5-di(adenosine-5')-pentaphosphate (an inhibitor of adenylate kinase) only ADP is effective. Also the release of accumulated Ca2+ observed when approximately 50% Mg2+ is discharged is retarded by bongkrekate and added Mg2+ whereas it is accelerated by atractylate. All adenine nucleotides have a significant effect in retarding the efflux of accumulated Ca2+ but, in the presence of oligomycin and P1,P5-di(adenosine-5')-pentaphosphate, only ADP is active. From these results we conclude that effluxes of Mg2+, Ca2+ and adenine nucleotide from rat liver mitochondria induced by external phosphate are interconnected and regulated by external ADP and Mg2+ levels.

Adenine Nucleotides↗

Insulin-lecithin interaction in non-aqueous solvents and its change after application of a static electric field.

The interaction between dipalmitoyl lecithin and egg lecithin with insulin was studied in a non-aqueous solvent such as dioxane-chloroform (1:1) by dielectric constant measurements and absorption spectra. The electrostatic character of the interaction results from the dielectric measurements and the effect of an external application of a static electric field (F = 30 kV/cm) is apparently related to the strength of such an interaction. The different strength of interaction of insulin with the two types of lecithins results also from experiments with a two-phase system.

Animals↗

Effect of physical training on carnitine concentration in liver, heart and gastrocnemius muscle of rat.

Physical training by compulsed swimming induces in rat heart a significant increase in the concentrations of carnitine and free carnitine but no detectable changes in liver and gastrocnemius muscle are observed. These results are consistent with the increased utilisation of fatty acid and pyruvate in trained animals and with an enhanced demand for carnitine by heart muscle.

Acetylcarnitine↗

Diamide effect on the hypertonic calcium uptake by rat red blood cells.

Red blood cells of rat exhibit an enhanced hypertonic calcium uptake after incubation with diazenedicarboxylic acids bis (N,N-dimethylamide) (diamide). Over the ranges reported in this paper the amount of membrane alteration is strongly and linearly dependent on the diamide concentration and on the osmolarity of the incubation medium. Treatment with 2,3-dihydroxy-1,4-dithiolbutane (dithioerythritol or DTE), after diamide removal, restores red blood cells calcium intake to values similar to those of the control. The results indicate that the sinergic action of diamide and hypertonicity can oxidize some thiol groups essential for the cation barrier maintenance.

Animals↗

Efflux of magnesium and potassium ions from liver mitochondria induced by inorganic phosphate and by diamide.

Addition to rat liver mitochondria of 2 mM inorganic phosphate or 0.15 mM diamide, a thiol-oxidizing agent, induced an efflux of endogenous Mg2+ linear with time and dependent on coupled respiration. No net Ca2+ release occurred under these conditions, while a concomitant release of K+ was observed. Mg2+ efflux mediated either by Pi or low concentration of diamide was completely prevented by EGTA, Ruthenium red, and NEM. These reagents also inhibited the increased rate of state 4 respiration induced both by Pi and diamide. At higher concentrations (0.4 mM), diamide induced an efflux of Mg2+ which was associated also with a release of endogenous Ca2+. Under these conditions EGTA completely prevented Mg2+ and K+ effluxes, while they were only partially inhibited by Ruthenium red and NEM. It is assumed that Mg2+ efflux, occurring at low diamide concentrations or in the presence of phosphate, is dependent on a cyclic in-and-out movement of Ca2+ across the inner mitochondrial membrane, in which the passive efflux is compensated by a continuous energy linked reuptake. This explains the dependence of Mg2+ efflux on coupled respiration, as well as the increased rate of state 4 respiration. The dependence of Mg2+ efflux on phosphate transport is explained by the phosphate requirement for Ca2+ movement.

Animals↗

Carnitine and acetylcarnitine in skeletal and cardiac muscle.

The acetylcarnitine/carnitine ratio has been found significantly increased in tibial muscles of swimming rats in comparison with normal rats. Analogous increase occurred in electrically stimulated tibial muscle in comparison with the unstimulated controlateral muscle of the same animal. Swimming also induced a statistically significant increase of the acetylcarnitine/carnitine ratio in heart, while norepinephrine administration resulted in a decrease of carnitine not accompanied by a corresponding increase in acetylcarnitine in a severe carnitine depletion of cardiac muscle. These results are discussed in terms of carnitine function in the acetyl metabolism, assuming the acetylcarnitine as a possible acetyl reservoir in the working muscle.

Acetylcarnitine↗