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Acid Accumulation (acid + accumulation)
Selected AbstractsPhytanic Acid Accumulation Is Associated with Conduction Delay and Sudden Cardiac Death in Sterol Carrier Protein-2/Sterol Carrier Protein-x Deficient MiceJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2004GEROLD MÖNNIG M.D. Introduction: The sterol carrier protein-2 gene encodes two functionally distinct proteins: sterol carrier protein-2 (SCP2, a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx, a peroxisomal thiolase known as peroxisomal thiolase-2), which is involved in peroxisomal metabolism of bile acids and branched-chain fatty acids. We show in this study that mice deficient in SCP2 and SCPx (SCP2null) develop a cardiac phenotype leading to a high sudden cardiac death rate if mice are maintained on diets enriched for phytol (a metabolic precursor of branched-chain fatty acids). Methods and Results: In 210 surface and 305 telemetric ECGs recorded in wild-type (C57BL/6; wt; n = 40) and SCP2 null mice (n = 40), no difference was observed at baseline. However, on diet, cycle lengths were prolonged in SCP2 null mice (262.9 ± 190 vs 146.3 ± 43 msec), AV conduction was prolonged (58.3 ± 17 vs 42.6 ± 4 ms), and QRS complexes were wider (19.1 ± 5 vs 14.0 ± 4 ms). In 11 gene-targeted Langendorff-perfused hearts isolated from SCP2 null mice after dietary challenge, complete AV blocks (n = 5/11) or impaired AV conduction (Wenckebach point 132 ± 27 vs 92 ± 10 msec; P < 0.05) could be confirmed. Monophasic action potentials were not different between the two genotypes. Left ventricular function studied by echocardiography was similar in both strains. Phytanic acid but not pristanic acid accumulated in the phospholipid fraction of myocardial membranes isolated from SCP2 null mice. Conclusion: Accumulation of phytanic acid in myocardial phospholipid membranes is associated with bradycardia and impaired AV nodal and intraventricular impulse conduction, which could provide an explanation for sudden cardiac death in this model. [source] Enhancement of Ca2+ -regulated exocytosis by indomethacin in guinea-pig antral mucous cells: arachidonic acid accumulationEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Shoko Fujiwara Ca2+ -regulated exocytosis is enhanced by an autocrine mechanism via the PGE2,cAMP pathway in antral mucous cells of guinea-pigs. The inhibition of the PGE2,cAMP pathway by H-89 (an inhibitor of protein kinase A, PKA) or aspirin (ASA, an inhibitor of cyclo-oxygenase, COX) decreased the frequency of ACh-stimulated exocytotic events by 60%. Indomethacin (IDM, an inhibitor of COX), however, decreased the frequency of ACh-stimulated exocytotic events only by 30%. Moreover, IDM increased the frequency of ACh-stimulated exocytotic events by 50% in H-89-treated or ASA-treated cells. IDM inhibits the synthesis of Prostaglandin (PGG/H) and (15R)-15-hydroxy-5,8,11 cis-13-trans-eicosatetraenoic acid (15R-HPETE), while ASA inhibits only the synthesis of PGG/H. Thus, IDM may accumulate arachidonic acid (AA). AACOCF3 or N -(p -amylcinnamoyl) anthranilic acid (ACA; both inhibitors of phospholipase A2, PLA2), which inhibits AA synthesis, decreased the frequency of ACh-stimulated exocytotic events by 60%. IDM, however, did not increase the frequency in AACOCF3 -treated cells. AA increased the frequency of ACh-stimulated exocytotic events in AACOCF3 - or ASA-treated cells, similar to IDM in ASA- and H-89-treated cells. Moreover, in the presence of AA, IDM did not increase the frequency of ACh-stimulated exocytotic events in ASA-treated cells. The PGE2 release from antral mucosa indicates that inhibition of PLA2 by ACA inhibits the AA accumulation in unstimulated and ACh-stimulated antral mucosa. The dose,response study of AA and IDM demonstrated that the concentration of intracellular AA accumulated by IDM is less than 100 nm. In conclusion, IDM modulates the ACh-stimulated exocytosis via AA accumulation in antral mucous cells. [source] Lead-dependent effects on arachidonic acid accumulation and the proliferation of vascular smooth muscleJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2002Robert V. Dorman Abstract Lead (Pb2+) has been implicated in the development of hypertension and atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a central feature of both conditions and there is evidence that Pb2+ potentiates serum-dependent cell growth. The aim of this work was to examine the role of phospholipase A2 in mitogen-dependent VSMC proliferation and determine if Pb2+ interacts with this system in order to potentiate mitotic events. It was observed that cell proliferation induced by angiotensin II, or fetal bovine serum, required the activation of a Ca2+ -dependent cytosolic phospholipase A2 and the subsequent release of unesterified arachidonic acid. This path was affected by Pb2+ as the metal increased the amount of arachidonic acid accumulation induced by either mitogen. In addition, Pb2+ potentiated mitogen-induced DNA synthesis when present at lower doses (0.02 or 0.2 mg%), but had no effect on DNA synthesis, or cell numbers, in unstimulated cells. However, a high dose (2 mg%) of Pb2+ attenuated the DNA synthesis stimulated by angiotensin II, or serum, but induced the accumulation of unesterified arachidonic acid in unstimulated cells. A biphasic effect of Pb2+ on cell numbers and viability was also observed as 0.02 or 0.2 mg% Pb2+ did not affect cell numbers or trypan blue exclusion in unstimulated cells, while 2 mg% Pb2+ reduced cell numbers and viability. It appeared, therefore, that the lower concentrations of Pb2+ increased arachidonic acid release and DNA synthesis only in stimulated VSMC, perhaps due to further activation of a Ca2+ -dependent processes. In contrast, the high dose of Pb2+ reduced DNA synthesis in stimulated cells and reduced cell numbers and viability in unstimulated cells, which may relate to the noted increase in unesterified arachidonic acid. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:245,253, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10045 [source] Effects of Fusaric Acid on Reactive Oxygen Species and Antioxidants in Tomato Cell CulturesJOURNAL OF PHYTOPATHOLOGY, Issue 10 2001E. Ku Generation of O2, and H2O2 as well as the activities of superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, dehydroascorbate reductase and ascorbate content were studied in tomato cell cultures in response to fusaric acid , a nonspecific toxin of phytopathogenic Fusarium species. Toxin treatment resulted in decreased cell viability which was preceded by culture medium alkalinization up to 0.65 pH unit and enhanced extracellular O2, production. The H2O2 level was not significantly affected. In toxin-treated cultures, a transient, significant increase occurred in intracellular superoxide dismutase, catalase, guaiacol peroxidase and ascorbate peroxidase activities. Fusaric acid-induced ascorbate turnover modulation led to up to a twofold increase in dehydroascorbic acid accumulation, and a decrease in the associated ascorbate redox ratio. It was concomitant with a significant decrease in dehydroascorbate reductase activity. These results support previous observations that the pro- and anti-oxidant systems are involved in response to fusaric acid treatment although differential response of H2O2 and its metabolism-related enzymes between the whole leaf and cell culture assays was found. [source] Nitric oxide-induced phosphatidic acid accumulation: a role for phospholipases C and D in stomatal closurePLANT CELL & ENVIRONMENT, Issue 2 2008AYELEN M. DISTÉFANO ABSTRACT Stomatal closure is regulated by a complex network of signalling events involving numerous intermediates, among them nitric oxide (NO). Little is known about the signalling events occurring downstream of NO. Previous studies have shown that NO modulates cytosolic calcium concentration and the activation of plasma membrane ion channels. Here we provide evidence that supports the involvement of the lipid second messenger phosphatidic acid (PA) in NO signalling during stomatal closure. PA levels in Vicia faba epidermal peels increased upon NO treatment to maximum levels within 30 min, subsequently decreasing to control levels at 60 min. PA can be generated via phospholipase D (PLD) or via phospholipase C (PLC) in concerted action with diacylglycerol kinase (DGK). Our results showed that NO-induced PA is produced via the activation of both pathways. NO-induced stomatal closure was blocked either when PLC or PLD activity was inhibited. We have shown that PLC- and PLD-derived PA represents a downstream component of NO signalling cascade during stomatal closure. [source] Prenatal diagnosis of free sialic acid storage disorders (SASD)PRENATAL DIAGNOSIS, Issue 8 2006Nina Aula Abstract Free sialic acid storage disorders, Salla disease (SD) and Infantile sialic acid storage disease (ISSD), are lysosomal storage diseases due to impaired function of a sialic acid transporter, sialin, at the lysosomal membrane. Several mutations of the sialin gene, SLC17A5, are known, leading either to the severe neonatal/infantile disease or to the milder, adult-type developmental disorder, Salla disease. Free sialic acid accumulation in lysosomes causes increased tissue concentration and consequently elevated urinary excretion. Prenatal diagnosis of SASD is possible either by determination of free sialic acid concentration or by mutation analysis of the SLC17A5 gene in fetal specimen, in chorionic villus biopsy particularly. Both techniques have been successfully applied in several cases, sialic acid assay more often in ISSD cases but mutation analysis preferentially in SD. Sialic acid assay of amniotic fluid supernatant or cultured amniotic fluid cells may give erroneous results and should not be used for prenatal diagnosis of these disorders. The present comments are mainly based on our experience of prenatal diagnosis of SD in Finnish families. A founder mutation in SLC17A5 gene, 115C-> T, represents 95% of the disease alleles in the Finnish SD patients, which provides a unique possibility to apply mutation analysis. Therefore, molecular studies have successfully been used in 17 families since the identification of the gene and the characterization of the SD mutations. Earlier, eight prenatal studies were performed by measuring the free sialic acid concentration in chorionic villus samples. Copyright © 2006 John Wiley & Sons, Ltd. [source] Assimilate transport in grapevines -effect of phloem disruptionAUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 3 2001J.J.(KOBUS) HUNTER Abstract Assimilate translocation in mature grapevines (cv. Gewürztraminer and cv. Harslevelü) under field conditions was investigated during the growth season by quantifying individual sugars and organic acids in mature leaves, shoot bark and berries, as affected by girdling the shoot just above the bunches. Tissue was sampled at berry set, pea size, veraison and ripeness stages of the vine. Invertase activity was determined in the shoot bark at ripeness. In the leaves, malic acid concentrations reached lowest levels at pea size, but increased thereafter. Tartaric acid decreased after peaking at pea size stage. Tartaric acid concentrations increased with girdling. Despite the increase in leaf age, sucrose concentrations remained virtually stable during the season, emphasising the importance of mature leaves for nourishing bunches. Girdling resulted in a build-up of sucrose in the leaves. In the bark, malic and tartaric acid stayed more or less the same during the growth period, but increased above the girdle. As a result of phloem disruption, sucrose also increased. The increase in glucose and tartaric acid is believed to result from catabolic cleavage of sucrose by invertase. Invertase activity was evident in the bark (of mature Harslevelü vines) at ripeness, which may indicate involvement in osmotic adjustments and gradients in the bark/phloem structure. In the berries, malic and tartaric acids reached peak concentrations at pea size. The volume increase during the ripening period, and in the case of malic acid also respiratory loss, resulted in a decrease in organic acid concentration. Malic acid continued to decrease after the initial decline, whereas tartaric acid stayed virtually stable. Girdling had no marked effect on organic acid accumulation in the berries. Sucrose concentrations were low during the first part of the season, but increased thereafter. Sucrose concentrations during ripening increased with girdling, which may represent a concentration effect and/or import from the rest of the vine. Sucrose concentrations (in mature Harslevelü vines) were indeed lower below than above the girdle. Comparison of sucrose concentrations in the leaves, bark and berries showed the existence of a decreasing concentration gradient, in line with the source:sink transport concept. An equally prominent decrease in sucrose:glucose ratio in the berries from the start of the ripening period indicates that vacuolar integrity (compartmentation) was affected in the ripening berry, most probably allowing hydrolysis of sucrose by invertase and decreasing osmotic potential within the berry. The results provide further evidence for the hypothesis of an osmotic gradient driven transport to the berry. [source] Microalgae for oil: Strain selection, induction of lipid synthesis and outdoor mass cultivation in a low-cost photobioreactorBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Liliana Rodolfi Abstract Thirty microalgal strains were screened in the laboratory for their biomass productivity and lipid content. Four strains (two marine and two freshwater), selected because robust, highly productive and with a relatively high lipid content, were cultivated under nitrogen deprivation in 0.6-L bubbled tubes. Only the two marine microalgae accumulated lipid under such conditions. One of them, the eustigmatophyte Nannochloropsis sp. F&M-M24, which attained 60% lipid content after nitrogen starvation, was grown in a 20-L Flat Alveolar Panel photobioreactor to study the influence of irradiance and nutrient (nitrogen or phosphorus) deprivation on fatty acid accumulation. Fatty acid content increased with high irradiances (up to 32.5% of dry biomass) and following both nitrogen and phosphorus deprivation (up to about 50%). To evaluate its lipid production potential under natural sunlight, the strain was grown outdoors in 110-L Green Wall Panel photobioreactors under nutrient sufficient and deficient conditions. Lipid productivity increased from 117 mg/L/day in nutrient sufficient media (with an average biomass productivity of 0.36 g/L/day and 32% lipid content) to 204 mg/L/day (with an average biomass productivity of 0.30 g/L/day and more than 60% final lipid content) in nitrogen deprived media. In a two-phase cultivation process (a nutrient sufficient phase to produce the inoculum followed by a nitrogen deprived phase to boost lipid synthesis) the oil production potential could be projected to be more than 90 kg per hectare per day. This is the first report of an increase of both lipid content and areal lipid productivity attained through nutrient deprivation in an outdoor algal culture. The experiments showed that this marine eustigmatophyte has the potential for an annual production of 20 tons of lipid per hectare in the Mediterranean climate and of more than 30 tons of lipid per hectare in sunny tropical areas. Biotechnol. Bioeng. 2009;102: 100,112. © 2008 Wiley Periodicals, Inc. [source] A preliminary neutron diffraction study of rasburicase, a recombinant urate oxidase enzyme, complexed with 8-azaxanthinACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2006Monika Budayova-Spano Crystallization and preliminary neutron diffraction measurements of rasburicase, a recombinant urate oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1,Å resolution using the LADI instrument from a crystal (grown in D2O) with volume 1.8,mm3. The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high-resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, urate oxidase has one of the largest primitive unit-cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106,Å) and molecular weights (135,kDa for the homotetramer) so far successfully studied with neutrons. [source] | |||||||||||||