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J Nordmann

Publications and source records attributed to J Nordmann.

At least 19 recordsLinked to original sources
PubMed1992

Sodium, calcium and exocytosis: confessions of calcified scientists.

Stimulated exocytotic secretion from nerve endings is initiated by an increase in intracellular free calcium concentration. We summarize here our latest findings regarding the temporal relationship between depolarization, elevation of [Ca2+]i and exocytosis in single vertebrate neuroendocrine nerve endings. In addition, we present surprising findings for a regulatory role of intracellular Na+ on exocytosis.

Animals↗
PubMed1986

Changes of fatty acid composition of phospholipids and lipid structural order in rat liver mitochondrial membrane subsequent to galactosamine intoxication. Effect of clofibrate.

Since it has been earlier reported that D-galactosamine induces an inhibition of palmitoylcarnitine transferase I and a depletion of mitochondrial phospholipids which were both prevented by clofibrate, an evaluation of the effects of these drugs on mitochondrial fatty acid composition was made. Galactosamine does not alter the fatty acid pattern of these fatty acids whereas clofibrate induces a 2-fold increase in monounsaturated/saturated fatty acids ratio and a 10-fold decrease of the 20:4 (n - 6)/20:3 (n - 6) ratio in phosphatidylcholine. These alterations suggest an increase of delta 9-desaturation and a decrease of delta 5-desaturation. To determine whether the drug-induced changes in mitochondrial phospholipids has an effect on the physical properties of the membrane, the lipid structural order of mitochondrial preparations was studied using the lipophilic probes DPH and TMA-DPH. Mitochondrial isolated either from galactosamine- or clofibrate-treated rats showed a decrease in fluorescence polarization, indicating an overall decrease in lipid structural order. This alteration is more drastic when both drugs are administered. This phenomenon suggests drastic changes in the bulk phase of inner mitochondrial membrane lipids after treatments and could explain the altered kinetic properties of palmitoylcarnitine transferase I.

Animals↗
PubMed1986

Preventive effect of clofibrate on carnitine palmitoyltransferase I inhibition and mitochondrial membrane phospholipid depletion induced by galactosamine.

We have previously reported that a D-galactosamine injection induces a decrease of carnitine palmitoyltransferase I activity correlated with a depletion of total phospholipid content in the mitochondrial membrane. The impact of a short-term clofibrate treatment on these membrane alterations is investigated, i.e., the kinetic properties of carnitine palmitoyltransferase I, including its sensitivity to malonyl-CoA and mitochondrial membrane content of the various phospholipids. A 4-day clofibrate treatment increases by 42% the apparent Km value of carnitine palmitoyltransferase I for palmitoyl-CoA, while the sensitivity of the enzyme to malonyl-CoA appears slightly decreased. Simultaneously, the cardiolipin content is increased by 70% in the mitochondrial membrane, whereas the phosphatidylethanolamine and phosphatidylcholine contents remain almost unaffected. This 4-day clofibrate treatment prevents the inhibition of carnitine palmitoyltransferase I activity subsequent to galactosamine administration but induces an increase in the apparent Km value for palmitoyl-CoA and a decrease of the sensitivity of the enzyme to malonyl-CoA. The contents of phospholipids which are decreased by galactosamine (phosphatidylcholine, -21%; phosphatidylethanolamine, -29%; cardiolipin, -40%) regain the control values when galactosamine administration is preceded by a clofibrate treatment. The data suggest that the clofibrate treatment counteracts the inhibition of activity of carnitine palmitoyltransferase I through the maintenance of mitochondrial membrane integrity.

Acyltransferases↗
PubMed1985

Effect of D-galactosamine in vitro on [U-14C]palmitate oxidation, triacylglycerol synthesis and secretion in isolated hepatocytes.

Isolated rat hepatocytes were used to study in vitro effects of 10 mM D-galactosamine (GalN) on hepatic fatty acids metabolism. At this concentration, membrane integrity and biochemical competence (i.e., gluconeogenesis and ureogenesis) remained unaffected. Protein synthesis and secretion, as measured by the incorporation of [U-14C]leucine into total and medium protein, was significantly inhibited when incubated for more than 2 h. GalN activated the incorporation of [U-14C]palmitate into triacylglycerols and depressed its utilization in the formation of labelled ketone bodies and 14CO2. Hepatocytes isolated from fasted rats exposed to GalN in vitro did not show any variation in prelabelled triacylglycerol secretion. GalN induced a rapid inhibition of prelabelled triacylglycerol secretion by hepatocytes isolated from fed rats in which this secretion occurred to a larger extent than in hepatocytes isolated from fasted rats. The data reported here suggest that GalN induces a rise of triacylglycerol synthesis by inhibiting the palmitate oxidation pathway and a decrease of triacylglycerol secretion through an early derangement of the secretory pathway.

Animals↗
PubMed1985

Discrepancy between the different subcellular activities of rat liver catalase and superoxide dismutases in response to acute ethanol administration.

After acute ethanol administration (2.3 g/kg) peroxisomal and extra-peroxisomal catalase activities were affected in opposite directions. As long as ethanol was present, peroxisomal catalase activity was enhanced, but unaffected by amino-triazole (AT) injection. Extra-peroxisomal catalase activity was decreased during the 24hr following ethanol administration and was also inhibited after AT injection. Whereas mitochondrial manganese-dependent superoxide dismutase (Mn-SOD) was unaffected, the cytosolic Cu,Zn-SOD activity was decreased. The time-course of this decrease suggests that acute ethanol administration affects primarily extra-peroxisomal catalase activity, thus rendering cytosolic superoxide dismutase more exposed to oxygen derivatives.

Alcoholic Intoxication↗
PubMed1983

Inhibition in vitro of acyl-CoA dehydrogenases by 2-mercaptoacetate in rat liver mitochondria.

In rat liver hypo-osmotically treated mitochondria, 2-mercaptoacetate inhibits respiration induced by palmitoyl-CoA, octanoate or butyryl-CoA only when the reaction medium is supplemented with ATP. Under this condition, NADH-stimulated respiration is not affected. In liver mitochondrial matrix, the presence of ATP is also required to observe a 2-mercaptoacetate-induced inhibition of acyl-CoA dehydrogenases tested with palmitoyl-CoA, butyryl-CoA or isovaleryl-CoA as substrate. As the oxidation of these substrates is also inhibited by the incubation medium resulting from the reaction of 2-mercaptoacetate with acetyl-CoA synthase, with conditions under which 2-mercaptoacetate has no effect, 2-mercaptoacetyl-CoA seems to be the likely inhibitory metabolite responsible for the effects of 2-mercaptoacetate. Kinetic experiments show that the main effect of the 2-mercaptoacetate-active metabolite is to decrease the affinities of fatty acyl-CoA dehydrogenases towards palmitoyl-CoA or butyryl-CoA and of isovaleryl-CoA dehydrogenase towards isovaleryl-CoA. Addition of N-ethylmaleimide to mitochondrial matrix pre-exposed to 2-mercaptoacetate results in the immediate reversion of the inhibitions of palmitoyl-CoA and isovaleryl-CoA dehydrogenations and in a delayed reversion of butyryl-CoA dehydrogenation. These results led us to conclude that (i) the ATP-dependent conversion of 2-mercaptoacetate into an inhibitory metabolite takes place in the liver mitochondrial matrix and (ii) the three fatty acyl-CoA dehydrogenases and isovaleryl-CoA dehydrogenase are mainly competitively inhibited by this compound. Finally, the present study also suggests that the inhibitory metabolite of 2-mercaptoacetate may bind non-specifically to, or induce conformational changes at, the acyl-CoA binding sites of these dehydrogenases.

Acyl Coenzyme A↗
PubMed1983

Carnitine palmitoyltransferase I. Inhibition by D-galactosamine and role of phospholipids.

Palmitate oxidation by liver mitochondria from rats treated with D-galactosamine (GalN) was markedly inhibited, 3 h after administration. The mitochondrial defect responsible for this inhibition was shown to be an inhibition of the activity of palmitoylcarnitine transferase I (EC 2.3.1.21). Apparent Km of the enzyme remained unchanged whereas apparent V was reduced by 30%. Addition of 10 mM GalN did not impair the activity of palmitoylcarnitine transferase I in mitochondria isolated from normal rats. Inhibition of palmitoylcarnitine biosynthesis by GalN treatment was completely reversed by phospholipid supply. At this stage of intoxication, mitochondrial phospholipid content was decreased whereas incorporation of [14C]palmitate into phospholipids in isolated hepatocytes was drastically inhibited: the phosphatidylcholine/phosphatidylethanolamine ratio was reduced by 33%. The results obtained from these studies show that the depletion of the phospholipid membrane content could account for the altered functional activity of palmitoylcarnitine transferase I.

Acyltransferases↗
PubMed1983

Hepatic lipid peroxidation and mitochondrial susceptibility to peroxidative attacks during ethanol inhalation and withdrawal.

Male Sprague-Dawley rats were exposed to increasing concentrations (15-22 mg/l) of ethanol vapor over a 4-day period. The hepatic lipid peroxide level as well as the sensitivity of mitochondria and microsomes to peroxidative attacks were studied during the early stage of alcohol intoxication, at the end of the inhalation period and, finally, during withdrawal. The level of hepatic lipid peroxide started to increase significantly after the first day of ethanol inhalation, whereas the in vitro mitochondrial sensitivity to peroxidation induced by ADP X Fe3+ in the presence of an O(2)-generating system was still unaltered after a 2-day inhalation period. Both the hepatic peroxide level and the mitochondrial sensitivity to peroxidation were significantly enhanced at the end of the 4-day inhalation period. Such an enhancement was still apparent 24 h after withdrawal, a time at which no more ethanol was present in the blood. Lipid peroxidation returned to normal values only 48 h after withdrawal. Microsomes were less affected than mitochondria by the ethanol treatment. It is suggested that the alterations of lipid peroxidation are related to the presence and/or the metabolism of ethanol at an early stage of inhalation, whereas changes in the membrane structure would be responsible for the maintenance of enhanced lipid peroxidation 24 h after ethanol withdrawal.

Animals↗
PubMed1983

Brain membrane disordering by administration of a single ethanol dose.

There is a bulk of evidence that ethanol exerts an important direct effect on biological membranes, especially in the central nervous system, during chronic administration. Whether membranes are affected after an acute and subacute ethanol administration remains to be demonstrated. Crude synaptic membrane fluidity (checked by fluorescence polarization) together with (Na+ +K+)ATPase activity were therefore examined 18 hours after a single oral ethanol administration (5 g/kg bwt.) to naive rats or to rats previously intubated with ethanol repeatedly during 4 days (increasing the daily dose from 7 to 10 g/kg). The sensitivity of both parameters to different concentrations of ethanol added in vitro (0.175 M-1.400 M) was also determined. Although no changes in the basal intrinsic fluidity were found, (Na+ +K+)ATPase activity increased slightly after administration of ethanol to naive as well as to short-term ethanol intoxicated rats. The fluidizing as well as the ATPase inhibiting effects following the addition of ethanol in vitro were markedly increased 18 hours after ethanol administration to naive rats. Such an hypersensitization seems not to be related to an unspecific stress or to changes in body temperature and was no longer apparent in short-term ethanol intoxicated rats. Disappearance of the acute ethanol induced hypersensitization with further ethanol administration may represent the first stage of tolerance acquisition.

Animals↗
PubMed1983

Liver superoxide dismutases and catalase during ethanol inhalation and withdrawal.

Manganese superoxide dismutase (Mn-SOD) studied during ethanol vapor inhalation shows no changes during the inhalation period (4 days) and a transient increase 12 hours after ethanol withdrawal. A significant decrease in cytosolic Cu-Zn-SOD is found at the end of the inhalation period and was sustained during 48 hours following ethanol withdrawal. It is suggested that this decrease in Cu-Zn-SOD activity might be related to an inactivation of the enzyme linked to the increase in hydroxyl radical production related to ethanol metabolism. Cytosolic catalase is reduced at the end of the ethanol inhalation period. This decrease could be related to an enhanced superoxide radical concentration linked to the reduced Cu-Zn-SOD activity.

Alcohol Withdrawal Delirium↗
PubMed1982

Effects of 2-mercaptoacetate in isolated liver mitochondria in vitro. Competitive inhibition of 3-hydroxybutyrate dehydrogenase and depression of the beta-oxidation pathway.

The effects of 2-mercaptoacetate on the respiration rates induced by different substrates were studied in vitro in isolated liver mitochondria. With palmitoyl-L-carnitine or 2-oxoglutarate as the substrate, the ADP-stimulated respiration (State 3) was dose-dependently inhibited by 2-mercaptoacetate. with glutamate or succinate as the substrate. State-3 respiration was only slightly inhibited by 2-mercaptoacetate. In contrast, the oxidation rate of 3-hydroxybutyrate was competitively inhibited by 2-mercaptoacetate in both isolated mitochondria and submitochondrial particles. In uncoupled mitochondria and in mitochondria in which ATP- and GTP-dependent acyl-CoA biosynthesis was inhibited, the inhibitory effect of 2-mercaptoacetate on palmitoyl-L-carnitine oxidation was abolished; under the same conditions, however, inhibition of 3-hydroxybutyrate oxidation by 2-mercaptoacetate still persisted. These results led to the following conclusions: 2-mercaptoacetate itself enters the mitochondrial matrix, inhibits fatty acid oxidation through a mechanism requiring an energy-dependent activation of 2-mercaptoacetate and itself inhibits 3-hydroxybutyrate oxidation through a competitive inhibition of the membrane-bound 3-hydroxybutyrate dehydrogenase. This study also strongly suggests that the compound responsible for the inhibition of fatty acid oxidation is 2-mercaptoacetyl-CoA.

3-Hydroxybutyric Acid↗
PubMed1982

Existence of an adenosine 5'-triphosphate dependent proton translocase in bovine neurosecretory granule membrane.

The addition of ATP to bovine neurohypophysial secretory granules suspended in isotonic sucrose medium induces a positive polarization, delta psi, of their interior without affecting their internal pH. In KCl-containing media, ATP failed to generate large delta psi but induced a pH gradient (delta pH; interior acidic). These observations are consistent with the existence in the neurosecretory granule membrane of an ATP-dependent inward electrogenic H+ translocase (H+ pump), capable in KCl-containing media of acidifying the granule matrix by H+-Cl- cotransport. The delta psi and delta pH generated by the H+ pump, defined as the ATP-induced changes sensitive to the H+ ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), were blocked by N,N'-dicyclohexylcarbodiimide, an inhibitor of all H+ pumps, and were insensitive to oligomycin, a mitochondrial ATPase inhibitor. In sucrose medium, measurements were complicated by a Donnan equilibrium reflecting the presence in the granule of peptide hormones and neurophysins which resulted in a CCCP-resistant resting delta pH. In KCl-containing media, the Donnan equilibrium was destroyed since the membrane is permeable to cations, but under these conditions a CCCP-resistant K+-diffusion potential was observed. The ATP-induced delta psi was also monitored by the extrinsic fluorescent probe bis(3-phenyl-5-oxoisoxazol-4-yl)pentamethine oxonol. The hypothesis of a granule H+ pump is further supported by the presence of an oligomycin-resistant ATPase in the preparation and the ultrastructural localization of such an activity on the granule membrane. The H+ pump has been found in both newly formed and aged neurosecretory granules. Its possible physiological function is discussed with reference to that of chromaffin granules, with which it has many similarities.

Adenosine Triphosphatases↗