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1.
Am J Med Sci ; 343(6): 446-51, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22173044

RESUMO

INTRODUCTION: Secretory phospholipases A2 (sPLA2) hydrolyze phospholipids in cell membranes and extracellular structures such as pulmonary surfactant. This study tests the hypothesis that sPLA2 are elevated in human lungs during acute respiratory distress syndrome (ARDS) and that sPLA2 levels are associated with surfactant injury by hydrolysis of surfactant phospholipids. METHODS: Bronchoalveolar lavage (BAL) fluid was obtained from 18 patients with early ARDS (<72 hours) and compared with samples from 10 healthy volunteers. Secreted phospholipase A2 levels were measured (enzyme activity and enzyme immunoassay) in conjunction with ARDS subjects' surfactant abnormalities including surfactant phospholipid composition, large and small aggregates distribution and surface tension function. RESULTS: BAL sPLA2 enzyme activity was markedly elevated in ARDS samples relative to healthy subjects when measured by ex vivo hydrolysis of both phosphatidylglycerol (PG) and phosphatidylcholine (PC). Enzyme immunoassay identified increased PLA2G2A protein in the ARDS BAL fluid, which was strongly correlated with the sPLA2 enzyme activity against PG. Of particular interest, the authors demonstrated an average depletion of 69% of the PG in the ARDS sample large aggregates relative to the normal controls. Furthermore, the sPLA2 enzyme activity against PG and PC ex vivo correlated with the BAL recovery of in vivo PG and PC, respectively, and also correlated with the altered distribution of the large and small surfactant aggregates. CONCLUSIONS: These results support the hypothesis that sPLA2-mediated hydrolysis of surfactant phospholipid, especially PG by PLA2G2A, contributes to surfactant injury during early ARDS.


Assuntos
Fosfatidilgliceróis/metabolismo , Fosfolipases A2 Secretórias/fisiologia , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/metabolismo , Líquido da Lavagem Broncoalveolar , Diagnóstico Precoce , Humanos , Hidrólise , Fosfatidilgliceróis/deficiência , Surfactantes Pulmonares/metabolismo , Síndrome do Desconforto Respiratório/enzimologia
2.
Plant Physiol ; 141(4): 1274-83, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16815953

RESUMO

Phosphatidylglycerol (PG) is a ubiquitous phospholipid in thylakoid membranes of cyanobacteria and chloroplasts and plays an important role in the structure and function of photosynthetic membranes. The last step of the PG biosynthesis is dephosphorylation of phosphatidylglycerophosphate (PGP) catalyzed by PGP phosphatase. However, the gene-encoding PGP phosphatase has not been identified and cloned from cyanobacteria or higher plants. In this study, we constructed a PG-deficient mutant from cyanobacterium Anabaena sp. PCC7120 with a disrupted gene (alr1715, a gene for Alr1715 protein, GenBank accession no. BAB78081) encoding a putative PGP phosphatase. The obtained mutant showed an approximately 30% reduction in the cellular content of PG. Following the reduction in the PG content, the photoautotrophical growth of the mutant was restrained, and the cellular content of chlorophyll was decreased. The decreases in net photosynthetic and photosystem II (PSII) activities on a cell basis also occurred in this mutant. Simultaneously, the photochemical efficiency of PSII was considerably declined, and less excitation energy was transferred toward PSII. These findings demonstrate that the alr1715 gene of Anabaena sp. PCC7120 is involved in the biosynthesis of PG and essential for photosynthesis.


Assuntos
Anabaena/enzimologia , Proteínas de Bactérias/genética , Monoéster Fosfórico Hidrolases/genética , Fotossíntese/fisiologia , Sequência de Aminoácidos , Anabaena/genética , Proteínas de Bactérias/metabolismo , Clonagem Molecular , Metabolismo dos Lipídeos , Dados de Sequência Molecular , Mutação , Fenótipo , Fosfatidilgliceróis/biossíntese , Fosfatidilgliceróis/deficiência , Monoéster Fosfórico Hidrolases/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Pigmentos Biológicos/metabolismo , Alinhamento de Sequência
3.
Mol Biol Cell ; 16(2): 665-75, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15563612

RESUMO

Disruption of PGS1, which encodes the enzyme that catalyzes the committed step of cardiolipin (CL) synthesis, results in loss of the mitochondrial anionic phospholipids phosphatidylglycerol (PG) and CL. The pgs1Delta mutant exhibits severe growth defects at 37 degrees C. To understand the essential functions of mitochondrial anionic lipids at elevated temperatures, we isolated suppressors of pgs1Delta that grew at 37 degrees C. One of the suppressors has a loss of function mutation in KRE5, which is involved in cell wall biogenesis. The cell wall of pgs1Delta contained markedly reduced beta-1,3-glucan, which was restored in the suppressor. Stabilization of the cell wall with osmotic support alleviated the cell wall defects of pgs1Delta and suppressed the temperature sensitivity of all CL-deficient mutants. Evidence is presented suggesting that the previously reported inability of pgs1Delta to grow in the presence of ethidium bromide was due to defective cell wall integrity, not from "petite lethality." These findings demonstrated that mitochondrial anionic lipids are required for cellular functions that are essential in cell wall biogenesis, the maintenance of cell integrity, and survival at elevated temperature.


Assuntos
Ânions/metabolismo , Cardiolipinas/metabolismo , Códon sem Sentido , Glicoproteínas/metabolismo , Mitocôndrias/química , Fosfatidilgliceróis/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Alelos , Sequência de Aminoácidos , Aminoglicosídeos/farmacologia , Antígenos de Bactérias/toxicidade , Cápsulas Bacterianas , Cardiolipinas/genética , Cardiolipinas/ultraestrutura , Sobrevivência Celular/genética , Parede Celular/química , Parede Celular/ultraestrutura , Quitina/análise , Quitina/metabolismo , Inibidores Enzimáticos/farmacologia , Corantes Fluorescentes , Deleção de Genes , Genes Fúngicos , Genes Supressores , Glicoproteínas/química , Glicoproteínas/genética , Glicoproteínas/ultraestrutura , Indóis , Mitocôndrias/metabolismo , Fosfatidilgliceróis/deficiência , Fosfatidilgliceróis/genética , Polissacarídeos Bacterianos/toxicidade , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/ultraestrutura , Temperatura , beta-Glucanas/análise , beta-Glucanas/química
4.
Am J Physiol Lung Cell Mol Physiol ; 288(4): L618-24, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15516491

RESUMO

Pulmonary surfactant's complex mixture of phospholipids and proteins reduces the work of breathing by lowering alveolar surface tension during respiration. One mechanism of surfactant damage appears to be the hydrolysis of phospholipid by phospholipases activated in the inflamed lung. Humans have several candidate secretory phospholipase A(2) (sPLA(2)) enzymes in lung cells and infiltrating leukocytes that could damage extracellular surfactant. We considered two mechanisms of surfactant disruption by five human sPLA(2)s, including generation of lysophospholipids and the depletion of specific phospholipids. All five sPLA(2)s studied ultimately caused surfactant dysfunction. Each enzyme exhibited a different pattern of hydrolysis of surfactant phospholipids. Phosphatidylcholine, the major phospholipid in surfactant and the greatest potential source for generation of lysophospholipids, was susceptible to hydrolysis by group IB, group V, and group X sPLA(2)s, but not group IIA or IID. Group IIA hydrolyzed both phosphatidylethanolamine and phosphatidylglycerol, whereas group IID was active against only phosphatidylglycerol. Thus, with groups IB and X, the generation of lysophospholipids corresponded with surfactant dysfunction. However, hydrolysis of and depletion of phosphatidylglycerol had a greater correlation with surfactant dysfunction for groups IIA and IID. Surfactant dysfunction caused by group V sPLA(2) is less clear and may be the combined result of both mechanisms.


Assuntos
Lisofosfolipídeos/metabolismo , Fosfatidilgliceróis/deficiência , Fosfolipases A/metabolismo , Tensoativos/metabolismo , Animais , Células COS/enzimologia , Humanos , Hidrólise , Pulmão/enzimologia , Fosfolipases A/classificação , Fosfolipases A/genética , Suínos
5.
Eur J Biochem ; 271(2): 329-38, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14717700

RESUMO

Two mutants of Chlamydomonas reinhardtii, mf1 and mf2, characterized by a marked reduction in their phosphatidylglycerol content together with a complete loss in its Delta3-trans hexadecenoic acid-containing form, also lost photosystem II (PSII) activity. Genetic analysis of crosses between mf2 and wild-type strains shows a strict cosegregation of the PSII and lipid deficiencies, while phenotypic analysis of phototrophic revertant strains suggests that one single nuclear mutation is responsible for the pleiotropic phenotype of the mutants. The nearly complete absence of PSII core is due to a severely decreased synthesis of two subunits, D1 and apoCP47, which is not due to a decrease in translation initiation. Trace amounts of PSII cores that were detected in the mutants did not associate with the light-harvesting chlorophyll a/b-binding protein antenna (LHCII). We discuss the possible role of phosphatidylglycerol in the coupled process of cotranslational insertion and assembly of PSII core subunits.


Assuntos
Chlamydomonas reinhardtii/genética , Complexos de Proteínas Captadores de Luz/metabolismo , Mutação/genética , Fosfatidilgliceróis/deficiência , Complexo de Proteína do Fotossistema II/biossíntese , Biossíntese de Proteínas , Animais , Chlamydomonas reinhardtii/metabolismo , Cloroplastos , Cruzamentos Genéticos , Luz , Mutagênese Insercional , Ácidos Palmíticos/metabolismo , Fenótipo , Fotossíntese , Preconceito
6.
J Lab Clin Med ; 127(3): 263-71, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9273359

RESUMO

Surfactant abnormalities may contribute to the impairment of gas exchange observed in Pneumocystis carinii pneumonia. Analysis of rat bronchoalveolar lavage (BAL) lipid extracts from normal controls, steroid controls, trimethaprim-sulfamethoxazole (TMP-SMX) controls, TMP-SMX/P. carinii pneumonia controls, and P. carinii pneumonia animals reveal similar total phospholipid and total protein levels. However, there was a marked reduction in phosphatidylglycerol (PG) from the BAL of P. carinii pneumonia rats as compared with control animals, with a decrease from 4.91 +/- 1.29 nmol/mg protein to 0.46 +/- 0.57 nmol/mg protein (p<0.05) and a decrease, as a percent of total phospholipids, from 7.7% +/- 0.88% to 0.91% +/- 0.59% (p<0.001). Furthermore, in vitro surface activities of BAL lipid extracts from control and P. carinii pneumonia rats revealed minimum surface tension increases from 9.38 +/- 1.71 mN/m in controls to 16.36 +/- 0.83 mN/m in P. carinii pneumonia rats (p<0.05) and likewise maximum surface tension increases from 22.14 +/- 4.34 mN/m to 38.57 +/- 2.07 mN/m (p<0.01). Of interest, the surface activity of PG-deficient P. carinii pneumonia BAL lipid extracts is completely restored to that of normal controls by the addition of exogenous PG. These findings suggest that a functionally abnormal surfactant occurs in P. carinii pneumonia and that this may account, in part, for the impairment of gas exchange observed in this disorder.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Fosfolipídeos/fisiologia , Pneumonia por Pneumocystis/fisiopatologia , Animais , Feminino , Terapia de Imunossupressão , Lipídeos/análise , Fosfatidilgliceróis/deficiência , Fosfatidilgliceróis/farmacologia , Fosfolipídeos/análise , Ratos , Ratos Endogâmicos Lew , Fatores de Tempo
7.
Exp Lung Res ; 11(3): 195-207, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3780601

RESUMO

To test the hypothesis that the deficit of fetal lung surfactant phosphatidylglycerol (PG) in diabetic pregnancies was due to increased plasma myo-inositol, lung PG content and plasma myo-inositol level were compared in fetuses of streptozotocin-diabetic rats and in fetuses of rats injected with myo-inositol during the 4 last gestational days. An inverse linear correlation was established between circulating myo-inositol and lung phosphatidylglycerol content, including data from fetuses of diabetic rats, which is consistent with the hypothesis. Changes in phospholipid synthetic rates were estimated in fetuses of rats given myo-inositol by measuring incorporation of labelled glycerol on a six hour period on the 21st gestational day, after i.v. injection to the mother. Incorporation into PG was 2.5 times smaller but incorporation into PI or PC were not modified. Pulmonary function in PG-deficient newborns of rats given a high-dosage myo-inositol was assessed by pressure/volume measurements on the lung in situ and by measurement of oxygen tension in aortic blood. Opening pressure of alveoli for lung inflation was increased and blood oxygenation was reduced (30%) in newborns with PG-deficient surfactant as compared with controls, thus suggesting an important physiological role for surfactant PG at birth.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Inositol/sangue , Pulmão/metabolismo , Fosfatidilgliceróis/biossíntese , Gravidez em Diabéticas/metabolismo , Animais , Animais Recém-Nascidos , Radioisótopos de Carbono , Feminino , Glicerol/metabolismo , Pulmão/embriologia , Fosfatidilgliceróis/deficiência , Fosfolipídeos/metabolismo , Gravidez , Surfactantes Pulmonares/metabolismo , Ratos , Ratos Endogâmicos
8.
Pediatr Res ; 19(3): 286-92, 1985 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3838583

RESUMO

The possibility that pulmonary surfactant, characterized by a phosphatidylglycerol deficiency, as in early fetal life, might have inferior surface properties was evaluated. We obtained this specific surfactant from adult rabbits by withholding glucose and giving them an excess of myoinositol by mouth and intravenously. Controls were given a similar quantity of glucose. The myoinositol resulted in a drastic reduction of surfactant phosphatidylglycerol, from 7.2 to 0.3% of phospholipids, and a corresponding increase in phosphatidylinositol from 4.8 to 11.3%. In addition, the myoinositol treatment increased the myoinositol that was disaturated from 18.5 to 27.3% (p less than 0.05). The corresponding figures for disaturated phosphatidyl-choline were 56.0 and 60.5%, respectively (NS). The myoinositol treatment for 4 days increased the pool size of alveolar surfactant by 32% (p less than 0.01). The surface activity was studied with modified Wilhelmy balance and the pulsating bubble surfactometer. Surfactant containing phosphatidylinositol rather than phosphatidylglycerol was not inferior, as compared to surfactant that contained phosphatidylglycerol (minimum surface tension: 2.0 versus 2.2 mN X m-1; collapse rate at 10 nM X m-1: 1.85 versus 1.95 min-1; rate of adsorption from subphase to surface: 32 versus 35 mN X m-1 X 30 s-1), nor was there a difference in the ability of the two surfactants to improve lung stability of 27-day-old rabbit fetuses (air retention at 35 cm H2O: 1.8 versus 1.8 ml/30 g; air retention at 0 cm H20: 0.8 versus 0.9 ml/30 g). We conclude that phosphatidylinositol surfactant does not have inferior surface properties.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Fosfatidilgliceróis/deficiência , Surfactantes Pulmonares/análise , Animais , Ácidos Graxos/análise , Masculino , Fosfatidilcolinas/análise , Fosfatidiletanolaminas/análise , Fosfatidilgliceróis/análise , Fosfatidilinositóis/análise , Surfactantes Pulmonares/fisiologia , Coelhos
9.
Artigo em Inglês | MEDLINE | ID: mdl-6688614

RESUMO

We have investigated the effects of substituting phosphatidylinositol (PI) for phosphatidylglycerol (PG) on the functional properties of rabbit lung surfactant. We gave oral 10% glucose solution for 3 days to 11 rabbits and 10% inositol to 12 others. Lung lavage surfactant phospholipids were normal in both groups, except that PG was low and PI was high in the inositol group. Fatty acyl group distributions did not differ, except for a slight decrease of oleic acid in the inositol group. Electron microscopic examination showed normal surfactant structure in both. The time course of surfactant adsorption to an air-water interface was similar in both groups. Minimum surface tension after film compression was 4.0 +/- 0.8 mN . m-1 in the glucose group and 2.9 +/- 1.3 mN . m-1 in the inositol group (mean +/- SE). Surface potential-surface pressure isotherms were identical to within 12 mV. Arterial blood gases breathing air and 100% O2 were the same in both groups, as were pressure-volume curves of excised lungs, with both air and saline filling. The results suggest that, if acidic phospholipids are necessary for maintaining normal surfactant structure and surface properties, normal pressure-volume relationships, and normal gas exchange, then PI may substitute for PG.


Assuntos
Fosfatidilgliceróis/deficiência , Surfactantes Pulmonares/fisiologia , Animais , Masculino , Microscopia Eletrônica , Coelhos , Respiração , Propriedades de Superfície , Irrigação Terapêutica
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