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Papers by Marie-Paule Mingeot

Research paper thumbnail of Modulation of the in vitro activity of lysosomal phospholipase A1 by membrane lipids

Chemistry and Physics of Lipids, 2005

Lysosomal phospholipases play a critical role for degradation of cellular membranes after their l... more Lysosomal phospholipases play a critical role for degradation of cellular membranes after their lysosomal segregation. We investigated the regulation of lysosomal phospholipase A1 by cholesterol, phosphatidylethanolamine, and negatively-charged lipids in correlation with changes of biophysical properties of the membranes induced by these lipids. Lysosomal phospholipase A1 activity was determined towards phosphatidylcholine included in liposomes of variable composition using a whole-soluble lysosomal fraction of rat liver as enzymatic source. Phospholipase A1 activity was then related to membrane fluidity, lipid phase organization and membrane potential as determined by fluorescence depolarization of DPH, 31 P NMR and capillary electrophoresis. Phospholipase A1 activity was markedly enhanced when the amount of negatively-charged lipids included in the vesicles was increased from 10 to around 30% of total phospholipids and the intensity of this effect depended on the nature of the acidic lipids used (ganglioside GM1 < phosphatidylinositol ∼ phosphatidylserine ∼ phosphatidylglycerol ∼

Research paper thumbnail of Variability of extracellular vesicle release during storage of red blood cell concentrates is associated with differential membrane alterations, including loss of cholesterol-enriched domains

Frontiers in Physiology

Transfusion of red blood cell concentrates is the most common medical procedure to treat anaemia.... more Transfusion of red blood cell concentrates is the most common medical procedure to treat anaemia. However, their storage is associated with development of storage lesions, including the release of extracellular vesicles. These vesicles affect in vivo viability and functionality of transfused red blood cells and appear responsible for adverse post-transfusional complications. However, the biogenesis and release mechanisms are not fully understood. We here addressed this issue by comparing the kinetics and extents of extracellular vesicle release as well as red blood cell metabolic, oxidative and membrane alterations upon storage in 38 concentrates. We showed that extracellular vesicle abundance increased exponentially during storage. The 38 concentrates contained on average 7 × 1012 extracellular vesicles at 6 weeks (w) but displayed a ∼40-fold variability. These concentrates were subsequently classified into 3 cohorts based on their vesiculation rate. The variability in extracellula...

Research paper thumbnail of Interaction of the macrolide azithromycin with phospholipids. I. Inhibition of lysosomal phospholipase A1 activity

Azithromycin, the first clinically developed dicationic macrolide antibiotic, displays an excepti... more Azithromycin, the first clinically developed dicationic macrolide antibiotic, displays an exceptional accumulation in lysosomes of cultured cells. In fibroblasts incubated with 50 mg/1 (66.6 /zM), it induces a distinct lysosomal phospholipidosis as evidenced by biochemical and ultrastructural criteria, which strikingly resembles alterations described previously with gentamicin, a pentacationic aminoglycoside antibiotic which inhibits the lysosomal catabolism of phospholipids. We show that both drugs inhibit, in an equimolar manner, the activity of phospholipase A i (assayed for phosphatidylcholine, included in negatively charged liposomes), in a way consistent with the model of 'charge neutralization' proposed already for gentamicin (Mingeot-Leclercq et al., 1988, Biochem. Pharmacol. 37, 591). Both drugs bind to negatively charged liposomes. Yet, in spite of this binding, azithromycin does not induce aggregation or fusion of negatively charged vesicles, under conditions in which gentamicin (or spermine, a fully hydrophilic polycation) causes a massive aggregation, and bis(/3-diethylaminoethylether)hexestrol (a dicationic amphiphile) causes fusion. The molecular interactions of azithromycin with acidic phospholipids are further examined in a companion paper.

Research paper thumbnail of Apoptosis in Renal Proximal Tubules of Rats Treated with Low Doses of Aminoglycosides

Antimicrobial Agents and Chemotherapy, 2000

Kidney cortex apoptosis was studied with female Wistar rats treated for 10 days with gentamicin a... more Kidney cortex apoptosis was studied with female Wistar rats treated for 10 days with gentamicin and netilmicin at daily doses of 10 or 20 mg/kg of body weight and amikacin or isepamicin at daily doses of 40 mg/kg. Apoptosis was detected and quantitated using cytological (methyl green-pyronine) and immunohistochemical (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining, in parallel with a measurement of drug-induced phospholipidosis (cortical phospholipids and phospholipiduria), cortical proliferative response (3H incorporation in DNA and histoautoradiography after in vivo pulse-labeling with [3H]thymidine), and kidney dysfunction (blood urea nitrogen and creatinine). Gentamicin induced in proximal tubules a marked apoptotic reaction which (i) was detectable after 4 days of treatment but was most conspicuous after 10 days, (ii) was dose dependent, (iii) occurred in the absence of necrosis, and (iv) was nonlinearly correlated with the proliferative r...

Research paper thumbnail of Modulation of the in vitro activity of lysosomal phospholipase A1 by membrane lipids

Chemistry and physics …, 2005

Phospholipase A1 activity was markedly enhanced when the amount of negatively-charged lipids incl... more Phospholipase A1 activity was markedly enhanced when the amount of negatively-charged lipids included in the vesicles was increased from 10 to around 30% of total phospholipids and the intensity of this effect depended on the nature of the acidic lipids used (ganglioside GM1 ...

Research paper thumbnail of Comparative stability studies of antipseudomonal beta-lactams for potential administration through portable elastomeric pumps (home therapy for cystic fibrosis patients) and motor-operated syringes (intensive care units)

Antimicrobial Agents and Chemotherapy, Aug 1, 2002

Research paper thumbnail of Comparative stability studies of antipseudomonal beta-lactams for potential administration through portable elastomeric pumps (home therapy for cystic fibrosis patients) and motor-operated syringes (intensive care units)

Antimicrobial Agents and Chemotherapy, Aug 1, 2002

Research paper thumbnail of Modulation of the in vitro activity of lysosomal phospholipase A1 by membrane lipids

Chemistry and Physics of Lipids, 2005

Lysosomal phospholipases play a critical role for degradation of cellular membranes after their l... more Lysosomal phospholipases play a critical role for degradation of cellular membranes after their lysosomal segregation. We investigated the regulation of lysosomal phospholipase A1 by cholesterol, phosphatidylethanolamine, and negatively-charged lipids in correlation with changes of biophysical properties of the membranes induced by these lipids. Lysosomal phospholipase A1 activity was determined towards phosphatidylcholine included in liposomes of variable composition using a whole-soluble lysosomal fraction of rat liver as enzymatic source. Phospholipase A1 activity was then related to membrane fluidity, lipid phase organization and membrane potential as determined by fluorescence depolarization of DPH, 31 P NMR and capillary electrophoresis. Phospholipase A1 activity was markedly enhanced when the amount of negatively-charged lipids included in the vesicles was increased from 10 to around 30% of total phospholipids and the intensity of this effect depended on the nature of the acidic lipids used (ganglioside GM1 < phosphatidylinositol ∼ phosphatidylserine ∼ phosphatidylglycerol ∼

Research paper thumbnail of Variability of extracellular vesicle release during storage of red blood cell concentrates is associated with differential membrane alterations, including loss of cholesterol-enriched domains

Frontiers in Physiology

Transfusion of red blood cell concentrates is the most common medical procedure to treat anaemia.... more Transfusion of red blood cell concentrates is the most common medical procedure to treat anaemia. However, their storage is associated with development of storage lesions, including the release of extracellular vesicles. These vesicles affect in vivo viability and functionality of transfused red blood cells and appear responsible for adverse post-transfusional complications. However, the biogenesis and release mechanisms are not fully understood. We here addressed this issue by comparing the kinetics and extents of extracellular vesicle release as well as red blood cell metabolic, oxidative and membrane alterations upon storage in 38 concentrates. We showed that extracellular vesicle abundance increased exponentially during storage. The 38 concentrates contained on average 7 × 1012 extracellular vesicles at 6 weeks (w) but displayed a ∼40-fold variability. These concentrates were subsequently classified into 3 cohorts based on their vesiculation rate. The variability in extracellula...

Research paper thumbnail of Interaction of the macrolide azithromycin with phospholipids. I. Inhibition of lysosomal phospholipase A1 activity

Azithromycin, the first clinically developed dicationic macrolide antibiotic, displays an excepti... more Azithromycin, the first clinically developed dicationic macrolide antibiotic, displays an exceptional accumulation in lysosomes of cultured cells. In fibroblasts incubated with 50 mg/1 (66.6 /zM), it induces a distinct lysosomal phospholipidosis as evidenced by biochemical and ultrastructural criteria, which strikingly resembles alterations described previously with gentamicin, a pentacationic aminoglycoside antibiotic which inhibits the lysosomal catabolism of phospholipids. We show that both drugs inhibit, in an equimolar manner, the activity of phospholipase A i (assayed for phosphatidylcholine, included in negatively charged liposomes), in a way consistent with the model of 'charge neutralization' proposed already for gentamicin (Mingeot-Leclercq et al., 1988, Biochem. Pharmacol. 37, 591). Both drugs bind to negatively charged liposomes. Yet, in spite of this binding, azithromycin does not induce aggregation or fusion of negatively charged vesicles, under conditions in which gentamicin (or spermine, a fully hydrophilic polycation) causes a massive aggregation, and bis(/3-diethylaminoethylether)hexestrol (a dicationic amphiphile) causes fusion. The molecular interactions of azithromycin with acidic phospholipids are further examined in a companion paper.

Research paper thumbnail of Apoptosis in Renal Proximal Tubules of Rats Treated with Low Doses of Aminoglycosides

Antimicrobial Agents and Chemotherapy, 2000

Kidney cortex apoptosis was studied with female Wistar rats treated for 10 days with gentamicin a... more Kidney cortex apoptosis was studied with female Wistar rats treated for 10 days with gentamicin and netilmicin at daily doses of 10 or 20 mg/kg of body weight and amikacin or isepamicin at daily doses of 40 mg/kg. Apoptosis was detected and quantitated using cytological (methyl green-pyronine) and immunohistochemical (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining, in parallel with a measurement of drug-induced phospholipidosis (cortical phospholipids and phospholipiduria), cortical proliferative response (3H incorporation in DNA and histoautoradiography after in vivo pulse-labeling with [3H]thymidine), and kidney dysfunction (blood urea nitrogen and creatinine). Gentamicin induced in proximal tubules a marked apoptotic reaction which (i) was detectable after 4 days of treatment but was most conspicuous after 10 days, (ii) was dose dependent, (iii) occurred in the absence of necrosis, and (iv) was nonlinearly correlated with the proliferative r...

Research paper thumbnail of Modulation of the in vitro activity of lysosomal phospholipase A1 by membrane lipids

Chemistry and physics …, 2005

Phospholipase A1 activity was markedly enhanced when the amount of negatively-charged lipids incl... more Phospholipase A1 activity was markedly enhanced when the amount of negatively-charged lipids included in the vesicles was increased from 10 to around 30% of total phospholipids and the intensity of this effect depended on the nature of the acidic lipids used (ganglioside GM1 ...

Research paper thumbnail of Comparative stability studies of antipseudomonal beta-lactams for potential administration through portable elastomeric pumps (home therapy for cystic fibrosis patients) and motor-operated syringes (intensive care units)

Antimicrobial Agents and Chemotherapy, Aug 1, 2002

Research paper thumbnail of Comparative stability studies of antipseudomonal beta-lactams for potential administration through portable elastomeric pumps (home therapy for cystic fibrosis patients) and motor-operated syringes (intensive care units)

Antimicrobial Agents and Chemotherapy, Aug 1, 2002