1,720,984 research outputs found
In vivo effect of acetyl-L-carnitine on succinate oxidation, adenine nucleotide pool and lipid composition of synaptic and non-synaptic mitochondria from cerebral hemispheres of senescent rats
No full textThe effect of acetyl-L-carnitine on succinate oxidation, adenine nucleotide pool and lipid composition of synaptic and 'free', non-synaptic, mitochondria in cerebral hemispheres of senescent rats has been studied. Fisher rats (24- or 28-month-old) were treated with acetyl-L-carnitine (300 mg/kg body wt., intraperitoneally (i.p.)) 3 h before being killed. Oxygen consumption was measured using succinate as a substrate; adenine nucleotides and lipids were analyzed by high performance liquid chromatography (HPLC). Acetyl-L-carnitine reverses, in synaptic mitochondria, the age-related decrease in the respiratory control ratio due to a higher state 4 respiration rate. Administration of acetyl-L-carnitine to senescent rats does not affect the total adenine nucleotide pool of synaptic and non-synaptic mitochondria which was unchanged with age. Finally, pretreatment of senescent rats with acetyl-L-carnitine brings the cholesterol and phospholipid contents of synaptic mitochondria, reduced in senescent rats, to the adult level; pretreatment of adult rats has no such effect. Altogether these results suggest that acetyl-L-carnitine is able to reverse age-related deficits of brain mitochondria
Deviant energetic metabolism of glycolytic cancer cells.
No full textInternational audienceThe central glycolytic and oxidative pathways and the ATP-producing mechanisms differ in sane and malignant cells by their regulation and dynamics. Fast-growing, poorly-differentiated cancer cells characteristically show high aerobic glycolysis. In the same way, cholesterol biosynthesis, which occurs by normal pathways in tumors, is deficient in feed-back regulation and in sterol-transport mechanisms. Other metabolic ways are deficient, as for example, intramitochondrial aldehyde catabolism, at the origin of a possible acetaldehyde toxicity, which can be circumvented by the synthesis of an unusual and neutral product for mammalian cells acetoin, through tumoral pyruvate dehydrogenase. If most of the glycolytic pyruvate is deviated to lactate production, little of the remaining carbons enter a truncated Krebs cycle where citrate is preferentially extruded to the cytosol where it feeds sterol synthesis. Glutamine is the major oxidizable substrate by tumor cells. Inside the mitochondrion, it is deaminated to glutamate through a phosphate-dependent glutaminase. Glutamate is then preferentially transaminated to alpha-ketoglutarate that enters the Krebs cycle. Glutamine may be completely oxidized through the abnormal Krebs cycle only if a way of forming acetyl CoA is present: cytosolic malate entering mitochondria is preferentially oxidized to pyruvate + CO2 through an intramitochondrial NAD(P)(+)-malic enzyme, whereas intramitochondrial malate is preferentially oxidized to oxaloacetate through malate dehydrogenase, thus providing a high level of intramitochondrial substrate compartmentation. These and other regulatory aberrations in tumor cells appear to be reflections of a complex set of non-random phenotypic changes, initiated by expression of oncogenes.The central glycolytic and oxidative pathways and the ATP-producing mechanisms differ in sane and malignant cells by their regulation and dynamics. Fast-growing, poorly-differentiated cancer cells characteristically show high aerobic glycolysis. In the same way, cholesterol biosynthesis, which occurs by normal pathways in tumors, is deficient in feed-back regulation and in sterol-transport mechanisms. Other metabolic ways are deficient, as for example, intramitochondrial aldehyde catabolism, at the origin of a possible acetaldehyde toxicity, which can be circumvented by the synthesis of an unusual and neutral product for mammalian cells acetoin, through tumoral pyruvate dehydrogenase. If most of the glycolytic pyruvate is deviated to lactate production, little of the remaining carbons enter a truncated Krebs cycle where citrate is preferentially extruded to the cytosol where it feeds sterol synthesis. Glutamine is the major oxidizable substrate by tumor cells. Inside the mitochondrion, it is deaminated to glutamate through a phosphate-dependent glutaminase. Glutamate is then preferentially transaminated to alpha-ketoglutarate that enters the Krebs cycle. Glutamine may be completely oxidized through the abnormal Krebs cycle only if a way of forming acetyl CoA is present: cytosolic malate entering mitochondria is preferentially oxidized to pyruvate + CO2 through an intramitochondrial NAD(P)(+)-malic enzyme, whereas intramitochondrial malate is preferentially oxidized to oxaloacetate through malate dehydrogenase, thus providing a high level of intramitochondrial substrate compartmentation. These and other regulatory aberrations in tumor cells appear to be reflections of a complex set of non-random phenotypic changes, initiated by expression of oncogenes
Biochemical, genetic, and metabolic adaptations of tumor cells that express the typical multidrug-resistance phenotype. Reversion by new therapies.
No full textInternational audienceAmong the genetic and metabolic alterations that cancer cells undergo, several allow their survival under extreme environmental conditions. The resulting aberrant metabolism is compatible with tumor progression at the expenses of high energy needs, especially for maintaining high division rate. When treated with chemotherapeutic drugs many cancer cells take advantage of their ability to develop a resistance phenotype, as part of an adaptative mechanism. Two main actors of this multidrug phenotype (MDR) are represented by the P-glycoprotein and by the more recently discovered multidrug-resistance associated protein (MRP), two membrane proteins of the ABC superfamily of transporters that can extrude chemotherapeutic drugs under an ATP-dependent mechanism. We will briefly review the major metabolic aberrations that several cancers develop, followed by the molecular, genetic, structural, and functional aspects related mainly to P-glycoprotein, with a concern for the regulation of mdr gene expression. We will point out the role that membrane cholesterol may play in the MDR phenotype, relate this phenotype to bioenergetic considerations, and review the ways of modulating it by the use of new therapeutic approaches.Among the genetic and metabolic alterations that cancer cells undergo, several allow their survival under extreme environmental conditions. The resulting aberrant metabolism is compatible with tumor progression at the expenses of high energy needs, especially for maintaining high division rate. When treated with chemotherapeutic drugs many cancer cells take advantage of their ability to develop a resistance phenotype, as part of an adaptative mechanism. Two main actors of this multidrug phenotype (MDR) are represented by the P-glycoprotein and by the more recently discovered multidrug-resistance associated protein (MRP), two membrane proteins of the ABC superfamily of transporters that can extrude chemotherapeutic drugs under an ATP-dependent mechanism. We will briefly review the major metabolic aberrations that several cancers develop, followed by the molecular, genetic, structural, and functional aspects related mainly to P-glycoprotein, with a concern for the regulation of mdr gene expression. We will point out the role that membrane cholesterol may play in the MDR phenotype, relate this phenotype to bioenergetic considerations, and review the ways of modulating it by the use of new therapeutic approaches
Isolated tumoral pyruvate dehydrogenase can synthesize acetoin which inhibits pyruvate oxidation as well as other aldehydes.
No full textInternational audienceOxidation of 1 mM pyruvate by Ehrlich and AS30-D tumor mitochondria is inhibited by acetoin, an unusual and important metabolite of pyruvate utilization by cancer cells, by acetaldehyde, methylglyoxal and excess pyruvate. The respiratory inhibition is reversed by other substrates added to pyruvate and also by 0.5 mM ATP. Kinetic properties of pyruvate dehydrogenase complex isolated from these tumor mitochondria have been studied. This complex appears to be able to synthesize acetoin from acetaldehyde plus pyruvate and is competitively inhibited by acetoin. The role of a new regulatory pattern for tumoral pyruvate dehydrogenase is presented.Oxidation of 1 mM pyruvate by Ehrlich and AS30-D tumor mitochondria is inhibited by acetoin, an unusual and important metabolite of pyruvate utilization by cancer cells, by acetaldehyde, methylglyoxal and excess pyruvate. The respiratory inhibition is reversed by other substrates added to pyruvate and also by 0.5 mM ATP. Kinetic properties of pyruvate dehydrogenase complex isolated from these tumor mitochondria have been studied. This complex appears to be able to synthesize acetoin from acetaldehyde plus pyruvate and is competitively inhibited by acetoin. The role of a new regulatory pattern for tumoral pyruvate dehydrogenase is presented
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Formation and utilization of acetoin, an unusual product of pyruvate metabolism by Ehrlich and AS30-D tumor mitochondria.
No full textInternational audience[14C]Pyruvate was rapidly non-oxidatively decarboxylated by Ehrlich tumor mitochondria at a rate of 40 nmol/min/mg of protein in the presence or absence of ADP. A search for decarboxylation products led to significant amounts of acetoin formed when Ehrlich tumor mitochondria were incubated with 1 mM [14C] pyruvate in the presence of ATP. Added acetoin to aerobic tumor mitochondria was rapidly utilized in the presence of ATP at a rate of 65 nmol/min/mg of protein. Citrate has been found as a product of acetoin utilization and was exported from the tumor mitochondria. Acetoin has been found in the ascitic liquid of Ehrlich and AS30-D tumor-bearing animals. These unusual reactions were not observed in control rat liver mitochondria.[14C]Pyruvate was rapidly non-oxidatively decarboxylated by Ehrlich tumor mitochondria at a rate of 40 nmol/min/mg of protein in the presence or absence of ADP. A search for decarboxylation products led to significant amounts of acetoin formed when Ehrlich tumor mitochondria were incubated with 1 mM [14C] pyruvate in the presence of ATP. Added acetoin to aerobic tumor mitochondria was rapidly utilized in the presence of ATP at a rate of 65 nmol/min/mg of protein. Citrate has been found as a product of acetoin utilization and was exported from the tumor mitochondria. Acetoin has been found in the ascitic liquid of Ehrlich and AS30-D tumor-bearing animals. These unusual reactions were not observed in control rat liver mitochondria
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