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Biomedical subjects

A Toninello

Publications and source records attributed to A Toninello.

At least 55 records · Page 3Linked to original sources
PubMed1986

Action of spermine on phosphate transport in liver mitochondria.

Spermine, at concentrations similar to those normally present in the cytosol of liver cells, facilitates the transport of phosphate into mitochondria and thus its accumulation within the matrix space. Both mersalyl and N-ethylmaleimide (NEM) inhibit phosphate influx either in the absence or in the presence of spermine. These inhibitors also inhibit, but only partially, the efflux from mitochondria of phosphate generated within the matrix space by the hydrolysis of ATP induced by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or the valinomycin-K+ system. The inhibition of phosphate efflux by both mersalyl and NEM is almost completely removed, unlike that of phosphate influx, by spermine. The possibility that spermine may induce phosphate efflux by damaging mitochondrial membranes and consequently inducing an unspecific permeability to phosphate is excluded by the full restoration of transmembrane potential once FCCP has been removed by albumin. Since spermine does not react with either thiol groups or thiol group reagents, the simplest explanation of the reported results is that the pathway of phosphate efflux is distinct from that of phosphate influx.

Animals↗
PubMed1985

Stabilising action of carnitine on energy linked processes in rat liver mitochondria.

Rat liver mitochondria exposed to stressing conditions - ageing at room temperature, incubation in the presence of t-butyl hydroperoxide or damaging concentrations of Ca2+ and phosphate- undergo a rapid fall in their membrane potential (delta psi) with a concomitant release of endogenous Mg2+ and accumulated Ca2+. Addition of L-carnitine to the incubation medium considerably delays mitochondrial deenergization. A similar, though lower, protection has also been observed in L-carnitine pretreated and subsequently washed rat liver mitochondria. Furthermore mitochondria isolated from livers of starved rats, treated with L-carnitine 30 minutes before death and exposed to the same stressing conditions show similar delay in the decrease of delta psi and concurrent energy linked processes as compared with untreated animals. Both the in vitro and in vivo results strongly indicate that the stabilising action of L-carnitine on liver mitochondria is due to the removal of membrane bound long chain acyl CoA.

Animals↗
PubMed1985

Uptake of spermine by rat liver mitochondria and its influence on the transport of phosphate.

Spermine, a polyamine present in the mammalian cells at rather high concentration, has, among other actions, a remarkable stabilizing effect on mitochondria, functions which have generally been attributed to the capability of this and other polyamines to bind to membrane anionic sites. In the present paper evidence is provided that at physiological concentrations spermine may also be transported into rat liver mitochondrial matrix space, provided that mitochondria are energized and inorganic phosphate is simultaneously transported. The close dependence of spermine transport is also demonstrated by the concurrent efflux of spermine and inorganic phosphate when mitochondria preloaded with the two ionic species are deenergized either with uncouplers or respiratory chain inhibitors. Furthermore, Mersalyl, the known inhibitor of phosphate transport, prevents both spermine uptake and release. Mg2+ inhibits the transport of spermine conceivably by competing for the some binding sites on the mitochondrial membrane. The physiological significance of these results is discussed.

Animals↗
PubMed1984

Biochemical derangements in ischemic myocardium: the role of carnitine.

The most important biochemical derangements in ischemic myocardium are the decrease of energy rich phosphates (ATP and phosphocreatine) and intracellular acidosis, both of which contribute to a rapid loss of the contractile function. How and to which extent the alterations of carbohydrate and lipid metabolism are involved in these derangements is briefly discussed. In conditions of oxygen restriction the synchronism between the cytosolic and mitochondrial phase of carbohydrate metabolism is disrupted and beta-oxidation of long chain fatty acids is prevented. Consequently less ATP and more lactate is produced and fatty acids accumulate together with their activation products, acyl CoA in particular. In ischemia free carnitine is also decreased and the carnitine dependent functions (acyl transfer across mitochondrial membrane and pyruvate and alpha ketoglutarate dehydrogenase stimulation) impaired. The meaning of the altered carnitine dependent functions is considered together with the possible (demonstrated and supposed) metabolic effects of carnitine administration in cardiac ischemia.

Acyl Coenzyme A↗
PubMed1983

On the mechanism of citrate and isocitrate protective action on rat liver mitochondria.

Both citrate and isocitrate prevent the damage (efflux of endogenous Mg2+ and pyridine nucleotides, decay of delta psi and release of accumulated Ca2+) induced in rat liver mitochondria by Ca2+ and phosphate fluxes. Addition of fluorocitrate suppresses the action of isocitrate, but not that of citrate. The same results have been obtained with mitochondria isolated from animals treated with fluoroacetate. It is suggested that citrate directly and isocitrate by prior conversion into citrate exert the protective action by chelating and retaining Mg2+ within the mitochondria.

Animals↗
PubMed1983

On the mechanism by which Mg2+ and adenine nucleotides restore membrane potential in rat liver mitochondria deenergized by Ca2+ and phosphate.

The presence of ATP or ADP in the incubation medium prevents the collapse of membrane potential induced by external Ca2+ and phosphate. The same adenine nucleotides are unable to restore collapsed membrane potential unless Mg2+ are also added. Bongkrekate is also able to prevent the effects of external Ca2+ and phosphate and when added after membrane potential has collapsed strongly potentiates the restorative action of ATP or ADP. Atractyloside has an opposite effect.

Adenine Nucleotides↗
PubMed1983

On the relationship between calcium and phosphate transport, transmembrane potential and acetoacetate-induced oxidation of pyridine nucleotides in rat-liver mitochondria.

Acetoacetate addition to rat liver mitochondria induces a complete oxidation of pyridine nucleotides, a collapse of membrane potential, a release of mitochondrial Ca2+ and a loss of respiratory control only in the presence of external phosphate. Acetoacetate also enhances the efflux of mitochondrial Mg2+ promoted by phosphate. All these effects are not only prevented but also reversed, except the oxidation of pyridine nucleotides, by the combined addition of Mg2+, ADP and dithioerythritol to damaged mitochondria. It is concluded that acetoacetate, through the oxidation of mitochondrial pyridine nucleotides, potentiates the action of phosphate in altering the mitochondrial permeability barrier, which is closely dependent on the maintenance of membrane thiol groups in a reduced form.

Acetoacetates↗
PubMed1982

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↗
PubMed1981

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↗
PubMed1978

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↗