Biomedical subjects

E Chávez

Publications and source records attributed to E Chávez.

At least 19 recordsLinked to original sources

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↗

PubMed1992

Impairment by cyclosporin A of reperfusion-induced arrhythmias.

This study introduces the immunosuppressor, cyclosporin A, as a cardioprotective drug. This effect was analyzed during development of reperfusion/induced arrhythmias after 5-min period of coronary ligation in hearts of rats under anesthesia. The results indicate that cyclosporin, when given before coronary occlusion, at a dose of 20 mg/kg, effectively protects against the high incidence of arrhythmias and the fall in blood pressure induced by reperfusion. In addition, in inhibits the delivery of lactic dehydrogenase and creatine kinase enzymes to the plasma. We propose that the protective effect could be related with its well documented action to restrain Ca(2+)-induced damage of mitochondrial functions.

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

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↗

PubMed1987

Metabolite transport in mitochondria as a function of osmolarity.

The effect of increasing sucrose concentrations on some mitochondrial functions was studied. The results showed that high osmolarity inhibits oxidative phosphorylation as well as ATPase activity and ATP-dependent delta phi formation as a consequence of adenine nucleotide translocase inhibition. It is also shown that high osmolarity does not affect delta phi formation and energy-dependent Ca2+ uptake as driven by succinate oxidation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of membrane proteins showed a different reactivity to o-phenantroline/Cu2+ as function of osmolarity. It is proposed that high sucrose concentrations induce a collapse of the matrix compartment that results in a restricted diffusion of some metabolites.

Adenine Nucleotides↗

PubMed1987

The mechanism of lead-induced mitochondrial Ca2+ efflux.

Addition of Pb2+ to rat kidney mitochondria is followed by induction of several reactions: inhibition of Ca2+ uptake, collapse of the transmembrane potential, oxidation of pyridine nucleotides, and a fast release of accumulated Ca2+. When the incubation media are supplemented with ruthenium red, the effect of Pb2+ on NAD(P)H oxidation, membrane delta psi, and Ca2+ release are not prevented if malate-glutamate are the oxidizing substrates; however, the latter two lead-induced reactions are prevented by ruthenium red if succinate is the electron donor. It is proposed that in mitochondria oxidizing NAD-dependent substrates, Pb2+ induces Ca2+ release by promoting NAD(P)H oxidation and a parallel drop in delta psi due to its binding to thiol groups, located in the cytosol side of the inner membrane. In addition, it is proposed that with succinate as substrate, the Ca2+ -releasing effect of lead is due to the collapse of the transmembrane potential as a consequence of the uptake of Pb2+ through the calcium uniporter, since such effect is ruthenium red sensitive.

Animals↗

PubMed1987

Decreased exchange of adenine nucleotides in human placental mitochondria.

The purpose of this work was to study the exchange of adenine nucleotides in mitochondria isolated from human placenta tissue. The results indicate that ADP and ATP are translocated at a lower rate than those reported for rat liver mitochondria. It is proposed that the limited transport is due to the particular lipid composition of placental mitochondria membrane, which induces an arrest in membrane fluidity with the consequent restriction in adenine nucleotide translocase mobility.

Adenosine Diphosphate↗

PubMed1985

Evidence for the involvement of dithiol groups in mitochondrial calcium transport: studies with cadmium.

The effect of cadmium on some functions of mitochondria isolated from kidneys of rat was studied. Addition of cadmium chloride to mitochondria induced stimulation of both State 4 respiratory rate and ATPase activity, which are prevented by the addition of ruthenium red. We also show that cadmium inhibits competitively calcium translocation; this inhibitory effect of cadmium is reverted by the addition of dithiothreitol. From these results, it is proposed that, similarly to Ca2+, cadmium penetrates mitochondria and binds to a membrane dithiol group, which is essential for the translocation of the cation.

Animals↗

PubMed1985

Ionophoretic-like action of diflunisal.

It is shown that diflunisal, a derivative salicylic acid, causes uncoupling of oxidative phosphorylation owing to its property of carrying hydrogen ions through the inner mitochondrial membrane in such way that a short-circuit of protons is promoted. As a consequence of the above, the drug induces a decrease of the internal negative membrane potential and therefore the release of intramitochondrial calcium. In addition this report presents evidences that diflunisal behaves as a ionophore molecule since it induces cation extraction into an organic phase.

1-Butanol↗

PubMed1979