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Biomedical subjects

Anne Galinier

Publications and source records attributed to Anne Galinier.

At least 19 recordsLinked to original sources
PubMed2006

Interaction of GapA with HPr and its homologue, Crh: Novel levels of regulation of a key step of glycolysis in Bacillus subtilis?

In Bacillus subtilis cells, we identified a new partner of HPr, an enzyme of the glycolysis pathway, the glyceraldehyde-3-phosphate dehydrogenase GapA. We showed that, in vitro, phosphorylated and unphosphorylated forms of HPr and its homologue, Crh, could interact with GapA, but only their seryl-phosphorylated forms were able to inhibit its activity.

Bacillus subtilis↗
PubMed2006

Site specific changes of redox metabolism in adipose tissue of obese Zucker rats.

Adipose tissues are differently involved in lipid metabolism and obesity according to their type and location. Increasing reports stress on the impact of redox metabolism on obesity and metabolic syndrome. The aim of this work is to investigate the site-specific redox metabolism in three different adipose tissues and its changes occurring in obesity. We analysed enzymatic and non-enzymatic parameters, and focused on the reduced/oxidized glutathione and coenzyme Q couples. In lean compared with obese non-diabetic Zucker rats, interscapular brown fat seems well protected against oxidative stress and epididymal adipose tissue shows a more reduced glutathione redox state, associated with a higher susceptibility to lipophilic oxidative stress than inguinal adipose tissue. Epididymal adipose tissue redox metabolism significantly differs from inguinal one by its limited redox metabolism adaptation. Our results demonstrate site-specific managements of reactive oxygen species metabolism in obese Zucker rats. These results are not consistent with the classic deciphering of inflammatory situation and produce a new conception of the redox parameters implication in the development of the metabolic syndrome.

Adipose Tissue, Brown↗
PubMed2006

[Physiological and physiopathological consequences of mitochondrial reactive oxygen species].

Literature on reactive oxygen species (ROS) effects on cell biology and physiopathology is huge and appears to be controversial. This could be explained by the fact that very few studies take into account the real subcellular source of ROS production, their chemical nature and the intensity of their production. In spite of the importance of the other sites of ROS production in the cell, we decided to focus on mitochondrial ROS. Besides their key role in bioenergetics and ATP synthesis, mitochondria are one of the main sites of ROS generation within the cell. 80 % of intracellular superoxide anion is provided by the mitochondrial respiratory chain. Mitochondrial ROS production is closely associated with activity of the respiratory chain and is modulated by environmental factors which can induce constraints on respiratory chain components. Nutrient availability as well as oxygen pressure can both modulate mitochondrial ROS production. When moderately produced, ROS specifically regulate intracellular signalling pathways by reversible oxidation of proteins such as transcription factors or proteins kinases. In this way, they can trigger cell adaptation to environmental changes as modifications of energetic metabolism or hypoxia. Indeed, we demonstrated that mitochondrial ROS act as key elements in the control of white adipose tissue development by specific up-regulation of the anti-adipogenic transcription factor CHOP-10/GADD153. However, when they are produced at high level and in a chronic manner, mitochondrial ROS can also have deleterious effects by massive and irreversible oxidation of their principals targets i.e. lipids, DNA and proteins. In these conditions, mitochondrial ROS are involved in aging process and in pathological situations as metabolic disease.

Animals↗
PubMed2005

Adipose tissue proadipogenic redox changes in obesity.

The role of inflammation and oxidative stress in the development of obesity and associated metabolic disorders is under debate. We investigated the redox metabolism in a non-diabetic obesity model, i.e. 11-week-old obese Zucker rats. Antioxidant enzyme activities, lipophilic antioxidant (alpha-tocopherol, coenzymes Q) and hydrophilic antioxidant (glutathione, vitamin C) contents and their redox state (% oxidized form), were studied in inguinal white fat and compared with blood and liver. The adipose tissues of obese animals showed a specific higher content of hydrophilic molecules in a lower redox state than those of lean animals, which were associated with lower lipophilic molecule content and lipid peroxidation. Conversely and as expected, glutathione content decreased and its redox state increased in adipose tissues of rats subjected to lipopolysaccharide-induced systemic oxidative stress. In these in vivo models, oxidative stress and obesity thus had opposite effects on adipose tissue redox state. Moreover, the increase in glutathione content and the decrease of its redox state by antioxidant treatment promoted in vitro the accumulation of triglycerides in preadipocytes. Taken together and contrary to the emergent view, our results suggest that obesity is associated with an intracellular reduced redox state that promotes on its own the development of a deleterious proadipogenic process.

Adipose Tissue↗
PubMed2005

Site specific alterations of adipose tissue mitochondria in 3'-azido-3'-deoxythymidine (AZT)-treated rats: an early stage in lipodystrophy?

Although it is well accepted that treatment with nucleoside reverse transcriptase inhibitors (NRTIs) modifies fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examines the effects of chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) on the mitochondrial metabolism and the redox status management of rat white adipose tissues originating from two anatomical sites, as well as of the rat liver. Results showed that AZT treatment induced differential effects on the mitochondrial functions depending on the anatomical localisation. Indeed, in inguinal adipose tissue, a significant decrease in the cytochrome c oxidase activity and in the mitochondrial DNA (mtDNA) content was observed, whereas the activity of citrate synthase, a mitochondrial protein exclusively encoded by the nucleus, was not affected. In contrast, no significant change in these parameters could be detected for epididymal tissue and for liver. In parallel, no oxidative stress could be detected after treatment, for both white adipose tissues and for liver, even though treated liver exhibited several modifications in redox management. Taken together, these data demonstrate differential mitochondrial effects of AZT on subcutaneous versus visceral white adipose tissue. Moreover, the decrease in mitochondrial oxidative capacity of inguinal adipocyte consecutive to AZT treatment is not primarily due to an oxidative stress per se, but rather to a depletion of the mtDNA content per cell.

Adipose Tissue↗
PubMed2005

Reference range for micronutrients and nutritional marker proteins in cord blood of neonates appropriated for gestational ages.

BACKGROUND: Reference values of numerous micronutrients at different gestational ages (GA) have not been yet reported based on large series. AIMS: This study aimed to establish the reference range for zinc, copper, selenium, vitamin A, vitamin E, retinol binding protein, transthyretin, albumin, transferrin and ceruloplasmin in neonates and to give the profiles according to gestational age. STUDY DESIGN: A total of 510 infants appropriate for gestational age were included in the study. The determinations were done using the serum cord blood of 262 term and 248 preterm infants (gestational age of 37 to 42 and 26 to 36 weeks, respectively). RESULTS: All nutrients correlated significantly with birth weight and gestational age but different patterns were highlighted. Vitamin A, retinol binding protein and prealbumin showed a triphasic pattern with a cut-off at about 36 to 39 weeks. In this period, these parameters rised significantly (P<0.001). Albumin and selenium showed a biphasic pattern with a significant positive correlation (P<0.001) between weeks 26 to 38. Transferrin and ceruloplasmin associated with copper showed a continuous increase with GA (P<0.001). On the opposite, zinc and vitamin E decreased. Zinc showed a biphasic pattern with a significant negative correlation (P<0.001) between the 26th to 34th weeks. Vitamin E presented a triphasic pattern with a cut-off at about 32 to 35 weeks (P<0.001). CONCLUSION: The large number of data allow the build-up of reference ranges and charts for the evaluation of micronutrients and proteins in high-risk neonates.

Biomarkers↗
PubMed2005

[High-dose buprenorphine substitution during incarceration. Management of opiate addicts].

OBJECTIVE: To describe the social and medical profiles of incarcerated (in detention or after sentencing) opiate addicts, whether or not they had already begun substitution treatment at arrival, and assess the impact of high-dose buprenorphine substitution therapy on the health of prisoners and the course of their incarceration. METHODS: A prospective survey was conducted on opiate addicts on admission to prison and after 2 months of incarceration, from December 2001 to February 2003, in 6 prison centres in the South East of France. RESULTS: During incarceration, no significant difference (other than in medical follow-up) appeared between the prisoners receiving substitution treatment and those who went through withdrawal on arrival. The first group differed from the second in several respects: their occupational history before incarceration was less stable, their history of drug addiction and incarceration was more serious (injection, psychotropic use, number of prior incarcerations, early age at first incarceration). The buprenorphine patients also differed in their more intense use of medical follow-up before incarceration. CONCLUSION: The impact of buprenorphine substitution therapy during incarceration could not be demonstrated, but prisoners receiving this treatment had a substantially different profile than those who were not receiving treatment when they arrived in prison.

Adult↗
PubMed2005

Water-protein hydrogen exchange in the micro-crystalline protein crh as observed by solid state NMR spectroscopy.

We report site-resolved observation of hydrogen exchange in the micro-crystalline protein Crh. Our approach is based on the use of proton T2' -selective 1H-13C-13C correlation spectra for site-specific assignments of carbons nearby labile protein protons. We compare the proton T2' selective scheme to frequency selective water observation in deuterated proteins, and discuss the impacts of deuteration on 13C linewidths in Crh. We observe that in micro-crystalline proteins, solvent accessible hydroxyl and amino protons show comparable exchange rates with water protons as for proteins in solution, and that structural constraints, such as hydrogen bonding or solvent accessibility, more significantly reduce exchange rates.

Amino Acid Sequence↗
PubMed2005

YvcK of Bacillus subtilis is required for a normal cell shape and for growth on Krebs cycle intermediates and substrates of the pentose phosphate pathway.

The HPr-like protein Crh has so far been detected only in the bacillus group of bacteria. In Bacillus subtilis, its gene is part of an operon composed of six ORFs, three of which exhibit strong similarity to genes of unknown function present in many bacteria. The promoter of the operon was determined and found to be constitutively active. A deletion analysis revealed that gene yvcK, encoded by this operon, is essential for growth on Krebs cycle intermediates and on carbon sources metabolized via the pentose phosphate pathway. In addition, cells lacking YvcK acquired media-dependent filamentous or L-shape-like aberrant morphologies. The presence of high magnesium concentrations restored normal growth and cell morphology. Furthermore, suppressor mutants cured from these growth defects appeared spontaneously with a high frequency. Such suppressing mutations were identified in a transposon mutagenesis screen and found to reside in seven different loci. Two of them mapped in genes of central carbon metabolism, including zwf, which encodes glucose-6-phosphate dehydrogenase and cggR, the product of which regulates the synthesis of glyceraldehyde-3-phosphate dehydrogenase. All these results suggest that YvcK has an important role in carbon metabolism, probably in gluconeogenesis required for the synthesis of cell wall precursor molecules. Interestingly, the Escherichia coli homologous protein, YbhK, can substitute for YvcK in B. subtilis, suggesting that the two proteins have been functionally conserved in these different bacteria.

Bacillus subtilis↗
PubMed2005

[High-dose buprenorphine substitution during incarceration.]

MANAGEMENT OF OPIATE ADDICTS: OBJECTIVE: To describe the social and medical profiles of incarcerated (in detention or after sentencing) opiate addicts, whether or not they had already begun substitution treatment at arrival, and assess the impact of high-dose buprenorphine substitution therapy on the health of prisoners and the course of their incarceration. METHODS: A prospective survey was conducted on opiate addicts on admission to prison and after 2 months of incarceration, from December 2001 to February 2003, in 6 prison centres in the South East of France. RESULTS: During incarceration, no significant difference (other than in medical follow-up) appeared between the prisoners receiving substitution treatment and those who went through withdrawal on arrival. The first group differed from the second in several respects: their occupational history before incarceration was less stable, their history of drug addiction and incarceration was more serious (injection, psychotropic use, number of prior incarcerations, early age at first incarceration). The buprenorphine patients also differed in their more intense use of medical follow-up before incarceration. CONCLUSION: The impact of buprenorphine substitution therapy during incarceration could not be demonstrated, but prisoners receiving this treatment had a substantially different profile than those who were not receiving treatment when they arrived in prison.

Journal Article↗
PubMed2005

[Morphine prescription to terminal cancer patients suffering from severe pain: results of a French survey].

This study aimed to determine factors associated with the prescription of morphine to terminal cancer patients suffering from severe pain. A phone survey was conducted among a sample of French GPs, neurologists and oncologists. Two short clinical cases described a terminally-ill patient with either a peritoneal carcinosis and intestinal occlusion, or a lung cancer, and in both cases suffering from severe pain. Overall, 917 agreed to participate among the 1,743 physicians contacted (global response rate 53%). About half of respondents did not support the prescription of morphine if the patient had an intestinal occlusion. Beliefs toward morphine, uneasiness with terminally-ill patients, age and female gender were independently associated with reluctance to prescribe morphine in presented cases. Specialised training has not completely remove reluctance toward morphine prescription in end-of-life care. Non-medical factors correlated to such reluctance, and especially gender, deserve more attention.

Adult↗
PubMed2004

HPr kinase/phosphorylase, a Walker motif A-containing bifunctional sensor enzyme controlling catabolite repression in Gram-positive bacteria.

Carbon catabolite repression (CCR) in Gram-positive bacteria is regulated by the bifunctional enzyme HPr kinase/phosphorylase (HprK/P). This enzyme catalyses the ATP- as well as the pyrophosphate-dependent phosphorylation of Ser-46 in HPr, a phosphocarrier protein of a sugar transport and phosphorylation system. HprK/P also catalyses the pyrophosphate-producing, inorganic phosphate-dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P-Ser-HPr). P-Ser-HPr functions as catabolite co-repressor by interacting with the LacI/GalR-type repressor, catabolite control protein A (CcpA), and allowing it to bind to operator sites preceding catabolite-regulated transcription units. HprK/P thus indirectly controls the expression of about 10% of the genes of Gram-positive bacteria. The two antagonistic activities of HprK/P are regulated by intracellular metabolites, which change their concentration in response to the absence or presence of rapidly metabolisable carbon sources (glucose, fructose, etc.) in the growth medium. Biochemical and structural studies revealed that HprK/P exhibits no similarity to eukaryotic protein kinases and that it contains a Walker motif A (or P-loop) as nucleotide binding site. Interestingly, HprK/P has a structural fold resembling that in kinases phosphorylating certain low molecular weight substrates such as nucleosides, nucleotides or oxaloacetate. The structures of the complexes of HprK/P with HPr and P-Ser-HPr have also been determined, which allowed proposing a detailed mechanism for the kinase and phosphorylase functions of HprK/P.

Amino Acid Motifs↗
PubMed2003

Dimerization of Crh by reversible 3D domain swapping induces structural adjustments to its monomeric homologue Hpr.

The crystal structure of the regulatory protein Crh from Bacillus subtilis was solved at 1.8A resolution and showed an intertwined dimer formed by N-terminal beta1-strand swapping of two monomers. Comparison with the monomeric NMR structure of Crh revealed a domain swap induced conformational rearrangement of the putative interaction site with the repressor CcpA. The resulting conformation closely resembles that observed for the monomeric Crh homologue HPr, indicating that the Crh dimer is the active form binding to CcpA. An analogous dimer of HPr can be constructed without domain swapping, suggesting that HPr may dimerize upon binding to CcpA. Our data suggest that reversible 3D domain swapping of Crh might be an efficient regulatory mechanism to modulate its activity.

Amino Acid Sequence↗
PubMed2003

Regulation and mutational analysis of the HPr kinase/phosphorylase from Bacillus subtilis.

In most Gram-positive bacteria, catabolite repression is mediated by a bifunctional enzyme, the HPr kinase/phosphorylase (HprK/P). It has recently been shown that HprK/P could catalyze the phosphorylation of the protein HPr by using pyrophosphate (PP(i)) as a phosphate donor instead of ATP. Here we showed that, as for ATP, PP(i) binds to the enzyme with strong positive cooperativity. However, in contrast to ATP, PP(i) binding does not modify the fluorescence properties of the unique Trp residue of Bacillus subtilis HprK/P. In addition, to understand how two conserved motifs, namely, the P-loop and the specific signature of this family, participate in the three enzymatic activities of HprK/Ps (ATP-kinase, PP(i)-kinase, and phosphorylase), several site-directed mutants were generated. Whereas the three activities are mediated by the P-loop which is directly involved in the binding of ATP, PP(i), or Pi, the signature motif seems to be involved preferentially in the dephosphorylation reaction. On the basis of these results, we propose a model in which the binding of the allosteric activator FBP induces a conformational change of a central loop located above the active site of HprK/P, thereby allowing the ATP binding. However, this conformational change is not required for the binding of PP(i).

Adenosine Diphosphate↗