Biomedical subjects

C Zazueta

Publications and source records attributed to C Zazueta.

32 records · Page 2Linked to original sources

PubMed1994

Triphenyltin as inductor of mitochondrial membrane permeability transition.

The effect of triphenyltin on mitochondrial Ca2+ content was studied. It was found that this trialkyltin compound induces an increase in membrane permeability that leads to Ca2+ release, drop of the transmembrane potential, and efflux of matrix proteins. Interestingly, cyclosporin A was unable to inhibit triphenyltin-induced Ca2+ release. Based on these results it is proposed that the hyperpermeable state is produced by modification of 2.25 nmol of membrane thiol groups.

Animals↗

PubMed1994

On the role of ADP to increase the inhibitory effect of cyclosporin on mitochondrial membrane permeability transition.

This work reports an investigation which demonstrate that the addition of ADP is necessary to attain the protective effect of cyclosporin on the carboxyatractyloside-induced mitochondrial Ca2+ release. Evidence are presented which indicate that the effect of ADP is exerted by increasing the inhibitory action of cyclosporin on the enzyme cyclophilin.

Adenosine Diphosphate↗

PubMed1993

Ionophoretic-like properties of ketorolac for calcium.

Ketorolac is an analgesic drug known to induce its therapeutic effect by inhibiting prostaglandin synthesis. In this work we introduce the nonsteroidal antialgesic drug as a compound with ionophoretic properties for calcium ions, showing that ketorolac induces mitochondrial Ca++ release. This reaction did not depend on an uncoupler-like action, because the drug does not collapse the internal negative membrane potential nor does it affect oxidative phosphorylation. In addition, it is shown that ketorolac ferries calcium ions into energized liposomes and has a hydrophobic phase with an affinity constant of 4 x 10(-3). The therapeutic action of ketorolac is related to its ionophoretic properties in addition to its well known inhibitory effect on the cyclooxygenase enzyme.

Animals↗

PubMed1992

Fluorescamine-induced membrane permeability in mitochondria.

1. Addition of fluorescamine (75 microM) to mitochondria induced an increase in membrane permeability. 2. The leakiness of the inner mitochondrial membrane is characterized by extensive release of accumulated Ca2+, collapse of the transmembrane potential, mitochondrial swelling and efflux of matrix proteins, among them, malate dehydrogenase. 3. These effects were diminished by supplementing the media with 1 mM phosphate, and partially prevented by Mg2+. 4. These results indicate that the primary amino groups of membrane components contribute, partially, to the maintenance of the permeability barrier in mitochondria.

Animals↗

PubMed1991

Intramitochondrial K+ as activator of carboxyatractyloside-induced Ca2+ release.

The role of intramitochondrial K+ content on the increase in membrane permeability to Ca2+, as induced by carboxyatractyloside was studied. In mitochondria containing a high K+ concentration (83 nmol/mg), carboxyatractyloside induced a fast and extensive mitochondrial Ca2+ release, membrane de-energization, and swelling. Conversely, in K(+)-depleted mitochondria (11 nmol/mg), carboxyatractyloside was ineffective. The addition of 40 mM K+ to K(+)-depleted mitochondria restored the capability of atractyloside to induce an increase in membrane permeability to Ca2+ release. The determination of matrix free Ca2+ concentration showed that, at an external free-Ca2+ concentration of 0.8 microM, control mitochondria contained 3.9 microM of free Ca2+ whereas K(+)-depleted mitochondria contained 0.9 microM free Ca2+. It is proposed that intramitochondrial K+ affects the matrix free Ca2+ concentration required to induce a state of high membrane permeability.

Animals↗

PubMed1991

Calcium transport sensitive to ruthenium red in cytochrome oxidase vesicles reconstituted with mitochondrial proteins.

We describe a calcium transport that is sensitive to ruthenium red in liposomes reconstituted with mitochondrial extracts. This system is able to build an internally negative membrane potential, which allows the electrogenic influx of Ca2+ and Sr2+. Proteins with molecular weights higher than 35 kDa were incorporated to the vesicles, and enhanced the accumulation of the cation in an energy-dependent fashion.

Animals↗

PubMed1991

Protective role of chlorpromazine on lead-induced damage to heart mitochondria.

1. The protective effect of chlorpromazine (CPZ) on the toxic effects of lead in mitochondrial functions was studied. 2. The findings indicate that CPZ at a concentration of 50 microM protects heart mitochondria against lead-induced Ca2+ uptake inhibition. 3. In addition, CPZ inhibits the drop of the transmembrane potential, as well as mitochondrial swelling as induced by 10 microM Pb2+. 4. It is proposed that the protective effect of chlorpromazine can be due to its stabilizing action on biological membranes.

Animals↗

PubMed1991

Protective behavior of captopril on Hg(++)-induced toxicity on kidney mitochondria. In vivo and in vitro experiments.

Mercurials are known to induce morphological and functional modifications in kidney mitochondria. In this work we studied in vitro and in vivo the protective effect of captopril on the deleterious effect of Hg(++)-induced nonspecific membrane permeability changes to Ca++ and membrane de-energization. In vivo the administration of captopril prevented the toxic effects of mercury poisoning on membrane permeability, oxidative phosphorylation and Ca++ homeostasis. Moreover, captopril preserves kidney tissue morphology from Hg(++)-induced damage. The protective effect of captopril is most likely related to the existence of a sulfhydryl group in the drug.

Animals↗

PubMed1990

Dicyclohexylcarbodiimide as inducer of mitochondrial Ca2+ release.

The effect of the alkylating reagent dicyclohexylcarbodiimide (DCCD) on mitochondrial Ca2+ content was studied. The results obtained indicate that DCCD at a concentration of 100 microM induces mitochondrial Ca2+ efflux. This reaction is accompanied by an increasing energy drain on the system, stimulation of oxygen consumption, and mitochondrial swelling. These DCCD effects can be partially suppressed by supplementing the incubation medium with 1 mM phosphate. By electrophoretic analysis on polyacrylamide-sodium dodecyl sulfate, it was found that DCCD binds to a membrane component with an Mr of 20 to 29 kDa.

Animals↗

PubMed1989

Characterization by Hg2+ of two different pathways for mitochondrial Ca2+ release.

The addition of Hg2+ to loaded kidney mitochondria induces the fast release of the accumulated cation. The Ca2+-efflux reaction exhibits kinetics characteristics that depend on the extent of the binding of Hg2+ to the membrane. At high levels of Hg2+ bound (approx. 11 nmol/mg), Ca2+ efflux rate is highly insensitive to the temperature of incubation, and the efflux seems to be directly related to the internal free Ca2+ concentration. At these levels of bound Hg2+, accumulated Sr2+ is released with characteristics similar to those observed with Ca2+. At lower levels of Hg2+ binding (2.5 nmol/mg), the efflux reaction is highly dependent on the incubation temperature and on the internal free Ca2+ concentration; under these conditions Sr2+ is not released. NAD(P)H oxidation as induced by the low Hg2+ concentration is inhibited at the lower temperatures. Radiolabeled Hg2+ incorporates into two clearly defined regions of membrane proteins separated through sodium dodecyl sulfate gel electrophoresis. One of the regions corresponds to proteins of apparent high molecular mass (i.e., 150 kDa), and the other to proteins with apparent molecular masses of 37-25 kDa. Mitochondria incubated with 2 microM 203Hg2+ incorporate the radionuclide in proteins that have molecular masses of around 41 and 26 kDa. The results indicate that, depending on the amount of Hg2+ bound to the inner membrane, two clearly distinct Ca2+ release mechanisms can be distinguished.

Animals↗

PubMed1989

Extensive Ca2+ release from energized mitochondria induced by disulfiram.

The effect of the alcohol-deterrent drug, disulfiram, on mitochondrial Ca2+ content was studied. Addition of this drug (20 microM) to mitochondria induces a complete loss of accumulated Ca2+. The calcium release is accompanied by a collapse of the transmembrane potential, mitochondrial swelling, and a diminution of the NAD(P)H/NAD(P) radio. These effects of disulfiram depend on Ca2+ accumulation; thus, ruthenium red reestablished the membrane delta psi and prevents the oxidation of pyridine nucleotides. The binding of disulfiram to the membrane sulfhydryls appeared to depend on the metabolic state of mitochondria, as well as on the mitochondrial configuration. In addition, it is shown that modification of 9 nmol -SH groups per mg protein suffices to induce the release of accumulated Ca2+.

Adenosine Diphosphate↗

PubMed1989

Induction of mitochondrial Ca2+ uptake by mersalyl.

1. The addition of mersalyl to aged mitochondria from rat kidneys, is followed by induction of an ATP-driven Ca2+ uptake which is sensitive to Ruthenium Red. 2. This Ca2+ influx requires Mg2+, albumin, and is accomplished by membrane energization. 3. The activation of Ca2+ uptake by the mercurial in the presence of ATP can be explained if it is assumed that the inorganic phosphate generated by ATPase activity, and trapped in the matrix by the thiol reagent, provides the negative potential which results in an electrophoresis cation influx.

Adenosine Triphosphate↗

PubMedDate not supplied

[Captopril protection from the nephrotoxic effects of mercury].

The experiments referred to in this article point to the fact that relatively low concentrations of Hg2+ (5-10 mM) produce damage to the internal mitochondrial membrane. This damage results in the formation of ionic channels that allow the spontaneous effusion of Ca+2 from the matrix. Together with this, the formation of channels produce the balance of the chemo-osmotic gradient, resulting in the overcoming of the transmembrane potential and the uncoupling of oxidative phosphorylation. The experiments carried out in vivo, point to the fact mercury produces acute tubular necrosis of kidney tissue. These toxic effects produced by Hg2+ in vitro with the addition of 15 microM of the inhibition of the angiotensin converting enzyme, captopril. In vivo experiments show that intraperitoneal infection of captopril (40 mg/kg) completely protects from mitochondrial dysfunction produced by mercurial intoxication.

Animals↗

PubMedDate not supplied

[Ketorolac protection in damage due to myocardial ischemia and reperfusion].

This study shows that the nonsteroidal anti-inflammatory drug. Ketorolac, has an ionophore-like action for calcium, such a drug may transfer calcium through an hydrophobic phase. This property does not affect the respiratory rate of mitochondria. These results indicate that the ionophoretic effect is not due to an uncoupling action of Ketorolac. The effect of this compound was tested in a reperfusion model where it was observed that Ketorolac (1 mg/Kg weight) administered 30 min before an ischemic period was induced, reverts the arrhythmic effect of reperfusion. These results are in agreement with the analysis of the plasmatic concentrations of the enzymes creatine kinase and lactic dehydrogenase. It was found that the levels of such enzymes were lower in Ketorolac treated group, than in the untreated one. The results clearly indicate that Ketorolac prevents from the myocardial damage induced by reperfusion, probably by avoiding calcium overload in myocytes.

Animals↗