Готові списки джерел за темами / Efflux Capacity

Добірка наукової літератури з теми "Efflux Capacity"

Автор: Grafiati

Опубліковано: 2 березня 2024

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Статті в журналах з теми "Efflux Capacity"

Khera, Amit V., and Daniel J. Rader. "Cholesterol Efflux Capacity." Arteriosclerosis, Thrombosis, and Vascular Biology 33, no. 7 (July 2013): 1449–51. http://dx.doi.org/10.1161/atvbaha.113.301519.

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März, Winfried, and Andreas Ritsch. "Cholesterol Efflux Capacity." Journal of the American College of Cardiology 67, no. 21 (May 2016): 2488–91. http://dx.doi.org/10.1016/j.jacc.2016.04.005.

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Franssen, Remco, Alinda W. M. Schimmel, Sander I. van Leuven, Simone C. S. Wolfkamp, Erik S. G. Stroes, and Geesje M. Dallinga-Thie. "In Vivo Inflammation Does Not Impair ABCA1-Mediated Cholesterol Efflux Capacity of HDL." Cholesterol 2012 (April 24, 2012): 1–8. http://dx.doi.org/10.1155/2012/610741.

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HDL provides atheroprotection by facilitating cholesterol efflex from lipid-laden macrophages in the vessel wall. In vitro studies have suggested impaired efflux capacity of HDL following inflammatory changes. We assessed the impact of acute severe sepsis and mild chronic inflammatory disease on the efflux capacity of HDL. We hypothesize that a more severe inflammatory state leads to stronger impaired cholesterol efflux capacity. Using lipid-laden THP1 cells and fibroblasts we were able to show that efflux capacity of HDL from both patients with severe sepsis or with Crohn's disease (active or in remission), either isolated using density gradient ultracentrifugation or using apoB precipitation, was not impaired. Yet plasma levels of HDL cholesterol and apoA-I were markedly lower in patients with sepsis. Based on the current observations we conclude that inflammatory disease does not interfere with the capacity of HDL to mediate cholesterol efflux. Our findings do not lend support to the biological relevance of HDL function changes in vitro.

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Yano, Kouji, Ryunosuke Ohkawa, Megumi Sato, Akira Yoshimoto, Naoya Ichimura, Takahiro Kameda, Tetsuo Kubota, and Minoru Tozuka. "Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1 Cells." Journal of Lipids 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/9891316.

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Apolipoprotein A-I (apoA-I), the main protein component of high-density lipoprotein (HDL), has many protective functions against atherosclerosis, one of them being cholesterol efflux capacity. Although cholesterol efflux capacity measurement is suggested to be a key biomarker for evaluating the risk of development of atherosclerosis, the assay has not been optimized till date. This study aims at investigating the effect of different states of cells on the cholesterol efflux capacity. We also studied the effect of apoA-I modification by homocysteine, a risk factor for atherosclerosis, on cholesterol efflux capacity in different states of cells. The cholesterol efflux capacity of apoA-I was greatly influenced by the extent of differentiation of THP-1 cells and attenuated by excessive foam cell formation.N-Homocysteinylated apoA-I indicated a lower cholesterol efflux capacity than normal apoA-I in the optimized condition, whereas no significant difference was observed in the cholesterol efflux capacity between apoA-I in the excessive cell differentiation or foam cell formation states. These results suggest that cholesterol efflux capacity of apoA-I varies depending on the state of cells. Therefore, the cholesterol efflux assay should be performed using protocols optimized according to the objective of the experiment.

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Doonan, R. J., A. Hafiane, C. Lai, J. P. Veinot, J. Genest, and S. S. Daskalopoulou. "Cholesterol Efflux Capacity, Carotid Atherosclerosis, and Cerebrovascular Symptomatology." Arteriosclerosis, Thrombosis, and Vascular Biology 34, no. 4 (April 2014): 921–26. http://dx.doi.org/10.1161/atvbaha.113.302590.

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Objective— To investigate the association of cholesterol efflux capacity with carotid atherosclerosis and cerebrovascular disease. Approach and Results— Patients with high-grade carotid stenosis (n=154) were recruited from Vascular Surgery clinics and 9 healthy controls from the McGill University Health Network, Montreal, Canada. Cerebrovascular symptomatology history was obtained. Stenosis was assessed by carotid ultrasound. Fasting blood samples were collected and depleted of apolipoprotein B particles by polyethylene glycol precipitation from serum. Cholesterol efflux was determined by incubating apolipoprotein B–depleted serum in cAMP-stimulated J774 cells for 6 hours. Carotid specimens were classified by 2 vascular pathologists using the American Heart Association atheromatous plaque classification. Differences in efflux were assessed according to (1) stenosis, (2) American Heart Association classification, and (3) cerebrovascular symptomatology. Normalized efflux was significantly lower in patients with carotid atherosclerosis compared with controls (0.97±0.16 versus 1.5±0.46; P <0.0001). Efflux was inversely associated with stenosis; the odds ratio for 80% to 99% versus 50% to 79% stenosis of tertile 1 (lowest) versus tertile 3 (highest) of efflux was 3.78 (95% confidence interval, 1.18–12.06) after adjusting for age, sex, low-density lipoprotein, and high-density lipoprotein. There were significant differences in cholesterol efflux between American Heart Association fibroatheroma (Va, 0.91±0.13), mainly calcific (Vb, 0.97±0.15), and mainly fibrotic (Vc, 1.03±0.21; P =0.05). There were no significant differences in efflux according to symptomatology. Conclusions— Cholesterol efflux capacity is inversely associated with increasing carotid stenosis and is associated with more advanced carotid plaque morphology, suggesting that cholesterol efflux capacity may be a biomarker for severity of carotid atherosclerotic burden. Whether therapies targeting high-density lipoprotein quality could be useful for stabilizing carotid atherosclerosis needs to be assessed.

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Ma, Cheng-I. J., Jennifer A. Beckstead, Airlia Thompson, Anouar Hafiane, Rui Hao Leo Wang, Robert O. Ryan, and Robert S. Kiss. "Tweaking the cholesterol efflux capacity of reconstituted HDL." Biochemistry and Cell Biology 90, no. 5 (October 2012): 636–45. http://dx.doi.org/10.1139/o2012-015.

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Mechanisms to increase plasma high-density lipoprotein (HDL) or to promote egress of cholesterol from cholesterol-loaded cells (e.g., foam cells from atherosclerotic lesions) remain an important target to regress heart disease. Reconstituted HDL (rHDL) serves as a valuable vehicle to promote cellular cholesterol efflux in vitro and in vivo. rHDL were prepared with wild type apolipoprotein (apo) A-I and the rare variant, apoA-I Milano (M), and each apolipoprotein was reconstituted with phosphatidylcholine (PC) or sphingomyelin (SM). The four distinct rHDL generated were incubated with CHO cells, J774 macrophages, and BHK cells in cellular cholesterol efflux assays. In each cell type, apoA-I(M) SM-rHDL promoted the greatest cholesterol efflux. In BHK cells, the cholesterol efflux capacities of all four distinct rHDL were greatly enhanced by increased expression of ABCG1. Efflux to PC-containing rHDL was stimulated by transfection of a nonfunctional ABCA1 mutant (W590S), suggesting that binding to ABCA1 represents a competing interaction. This interpretation was confirmed by binding experiments. The data show that cholesterol efflux activity is dependent upon the apoA-I protein employed, as well as the phospholipid constituent of the rHDL. Future studies designed to optimize the efflux capacity of therapeutic rHDL may improve the value of this emerging intervention strategy.

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Dinnes, Donna Lee M., Stephen J. Nicholls, Wendy Jessup, and Leonard Kritharides. "HDL heterogeneity and serum efflux capacity." Current Opinion in Lipidology 26, no. 4 (August 2015): 350–52. http://dx.doi.org/10.1097/bor.0b013e32834b1fb1.

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Talbot, Charlotte P. J., Jogchum Plat, Andreas Ritsch, and Ronald P. Mensink. "Determinants of cholesterol efflux capacity in humans." Progress in Lipid Research 69 (January 2018): 21–32. http://dx.doi.org/10.1016/j.plipres.2017.12.001.

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Anastasius, Malcolm, Maaike Kockx, Wendy Jessup, David Sullivan, Kerry-Anne Rye, and Leonard Kritharides. "Cholesterol efflux capacity: An introduction for clinicians." American Heart Journal 180 (October 2016): 54–63. http://dx.doi.org/10.1016/j.ahj.2016.07.005.

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Rohatgi, Anand, and Scott M. Grundy. "Cholesterol Efflux Capacity as a Therapeutic Target." Journal of the American College of Cardiology 66, no. 20 (November 2015): 2211–13. http://dx.doi.org/10.1016/j.jacc.2015.09.012.

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Більше джерел

Дисертації з теми "Efflux Capacity"

Fournier, Natalie. "Modeles d'etude de la capacite d'efflux du cholesterol cellulaire par le serum : evaluation du role de trois acteurs du metabolisme lipoproteique : les phospholipides-hdl, la lcat et l'apolipoproteine aiv (doctorat : structure et fonctionnement des systemes biologiques integres)." Paris 11, 1998. http://www.theses.fr/1998PA114834.

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Beaudet, Marie-Lou. "Les effets du dalcetrapib, un inhibiteur de la protéine de transfert des esters de cholestérol (CETP), sur la structure et la fonction des lipoprotéines de haute densité (HDL) dans l’étude dal-PLAQUE2." Thèse, 2015. http://hdl.handle.net/1866/13867.

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Частини книг з теми "Efflux Capacity"

Turina, M. P., G. Venturoli, and B. A. Melandri. "Correlation Between Buffering Capacity and Proton Efflux in Bacterial Chromatophores." In Current Research in Photosynthesis, 1991–94. Dordrecht: Springer Netherlands, 1990. http://dx.doi.org/10.1007/978-94-009-0511-5_457.

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McCormack, James G., and Martin Crompton. "The Role and Study of Mammalian." In Cellular Calcium, 345–82. Oxford University PressOxford, 1991. http://dx.doi.org/10.1093/oso/9780199631315.003.0015.

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Abstract The inner membrane of mitochondria of mammalian, and perhaps of all vertebrate, tissues contains Ca2+ transport systems that mediate continuous Ca2+ cycling across the membrane (Figure I; see refs 1-3 for reviews). The cycle comprises a Ca2+ uniporter which allows passive Ca2+ entry down the Ca2+ electrochemical gradient and one, or possibly two, active egress mechanisms. The principal efflux mechanism involves obligatory exchange between Ca2+ and Na+ with the probable stoichiometry of 2Na+: 1Ca2\ this exchange is linked to the chemiosmotic H+ circuit via Na+:H+ exchange. Mitochondria may also contain a Na+-independent mechanism for Ca2+ efflux, although whether this involves direct Ca2+: H+ exchange is controversial. Although cycling of Ca2+involves the dissipation of the protonmotive gradient, under normal cellular conditions the calculated overall energy cost is less than 1% of the respiratory capacity of the mitochondria (1, 2).

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Kalle Kwaifa, Ibrahim, Abdullahi S. Mainasara, Muhammad Lawal Jidda, Amrina Mohammad Amin, Garba Abdullahi, Faruku Ladan, and Maryam Danyaro. "Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density Lipoprotein as a Molecular Modifier." In Non-alcoholic Fatty Liver Disease - New Insight and Glance Into Disease Pathogenesis. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.108199.

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The pathophysiology of non-alcoholic fatty liver disease (NAFLD) can be identified by modifications in lifestyle, diet and inflammation, all of which have significant implications for the severity of the clinicopathologic outcome of the disease. Prolonged accumulation of hepatic lipid may result in hepatic dysfunction, inflammation and advanced forms of NAFLD. NAFLD describes the presence of hepatic steatosis in the absence of alcohol use and other causes of liver disease. It covers a broad spectrum of hepatic histopathological alterations, from a non-inflammatory intracellular accumulation of fat to non-alcoholic steatohepatitis (NASH), which may progress to hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Previous evidence has shown that NAFLD is associated with a range of metabolic syndromes, including obesity, hyperlipidaemia, insulin resistance and diabetes. Hepatic fibrosis and cirrhosis are more common in people with NAFLD, which is partly associated with hyperlipidaemia and low high-density lipoprotein-cholesterol (HDL-C) levels. The ability of HDL to facilitate cholesterol efflux, as determined by cholesterol efflux capacity (CEC), has been linked to its hepatoprotective functions in the body. Findings have demonstrated that NAFLD patients have suppressed HDL CEC. This chapter summarizes the molecular mechanisms and pathogenesis involved in NAFLD. The role of HDL as a molecular modulator of NAFLD, clinical implications and the therapeutic targets to prevent NAFLD have also been discussed.

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Kameswaran, Srinivasan, and Bellamkonda Ramesh. "Natural QSIs for Biofilm Control in Pathogenic Bacteria." In Quorum Quenching, 105–26. Royal Society of Chemistry, 2023. http://dx.doi.org/10.1039/bk9781837671380-00105.

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Multidrug resistant strains of bacteria and fungi have emerged as a result of improper use of antibiotics in both humans and animals, despite the fact that the development of antibiotics has decreased morbidity and death caused by infectious diseases. Staphylococcus aureus is the pathogen of most concern when it comes to antibiotic resistance because of its inherent virulence, capacity to produce a high number of infections and ability to endure a variety of environmental circumstances. S. aureus has a variety of strategies to build antibiotic resistance, including the modification of drugs (β-lactamases), utilization of an alternate target site [penicillin binding protein 2a (PBP2a)], antibiotic efflux [norfloxacin resistance A (NorA)] and biofilm development. This has boosted interest in traditional medicine, which has been used for a long time to treat a variety of infectious diseases in various parts of the world. Because they include a complex blend of phytochemical components, plant extracts are a key source in the fight against microbial resistance because resistance to them develops extremely slowly. Additionally, phytochemical components found in plant extracts have anti-inflammatory and immunomodulatory properties. The goal of the current study is to energize efforts to find plant extracts and the phytochemicals they contain that can inhibit microbial resistance. In the future, S. aureus infections could be treated effectively and without evident adverse effects by using plant extracts and their purified ingredients.

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Shaikh, Ajam C., Ashfaq A. Shah, and Amit Gupta. "Nanocarriers: Promising Vehicles for Controlled Bioactive Drug Delivery in Current Medical System." In Medicinal Plants: Microbial Interactions, Molecular Techniques and Therapeutic Trends, 311–35. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815136838123010020.

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Nanomaterials have been widely employed in the medical profession in recent decades, thanks to the rapid development of nanotechnology. Their distinctive physical and chemical qualities, such as minimal size, functionalized surface characteristics, stable interactions with ligands, high carrier capacity, and ease of binding with both hydrophilic and hydrophobic substances have made them ideal platforms for the target-specific and controlled delivery of micro-and macromolecules in disease therapy and have revealed an excellent potential pertaining to clinical entities with the goal of fine-tuning bioavailability, bioefficacy, and pharmacokinetics. The absorption, post-administration stability as well as bioavailability of bioactive drugs and other medicinal substances are the key issues. Some critical medications have low gastrointestinal absorption and permeability in their active form, are inactivated by pH and temperature fluctuations and cause catastrophic off-target and undesirable side effects. Certain investigations have also indicated that active efflux mechanisms affect the absorption of some presently integrated compounds with structural alterations across the intestinal wall. Furthermore, intestinal bacteria and/or enzymes break down fragile structures of active substances into a variety of metabolites, each of which has different bioactivity than the original chemical compound. Nanocarrier-mediated distribution improved their solubilization potential, changed absorption paths, and reduced metabolic breakdown by gut bacteria and enzymes. Combining nanobiotechnology with current therapeutic techniques has shown to be effective in bringing innovative and previously rejected bioactive substances to the market for treating a myriad of diseases and disorders. As a result, we predict that nanotechnology will play a larger role in illness detection and treatment in the future, perhaps helping to overcome bottlenecks in current medical approaches. This chapter focuses on a comprehensive discussion of strategies and applications of nanoengineered delivery systems along with the pharmacokinetic properties and drug-delivery mechanism of these nanocarriers. Probably associated drawbacks, challenges, future advancements, and scopes of nanocarriers in clinical care are also highlighted.

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Тези доповідей конференцій з теми "Efflux Capacity"

Cacciapaglia, F., S. Perniola, J. Härdfeldt, M. Nivuori, O. Magazzino, MG Giannotta, M. Giannini, MG Anelli, A. Moschetta, and F. Iannone. "THU0143 Cholesterol efflux capacity of hdl is otherwise improved by different biologic-dmards in rheumatoid arthritis." In Annual European Congress of Rheumatology, 14–17 June, 2017. BMJ Publishing Group Ltd and European League Against Rheumatism, 2017. http://dx.doi.org/10.1136/annrheumdis-2017-eular.2680.

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Segura, B. Tejera, M. Macía-Díaz, JDM Machado, A. Vera-González de, A. González-Delgado, JM Olmos, JL Hernández, F. Díaz-González, MA González-Gay, and I. Ferraz-Amaro. "SAT0088 Hdl cholesterol efflux capacity in rheumatoid arthritis patients: contributing factors and relationship with subclinical atherosclerosis." In Annual European Congress of Rheumatology, 14–17 June, 2017. BMJ Publishing Group Ltd and European League Against Rheumatism, 2017. http://dx.doi.org/10.1136/annrheumdis-2017-eular.4100.

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Scanlon, T., P. Wilson, G. Priestman, and J. Tippetts. "Development of a Novel Flow Control Device for Limiting the Efflux of Air Through a Failed Pipe." In ASME Turbo Expo 2009: Power for Land, Sea, and Air. ASMEDC, 2009. http://dx.doi.org/10.1115/gt2009-59662.

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The secondary air-systems of a gas turbine engine frequently incorporate pipes and ducts to transport air for duties such as cooling and sealing of the turbine components, pressurisation of the aircraft cabin and component de-icing. The engine must be capable of operating safely in the event of failure of a pipe or duct. The ducts typically pass through the low pressure ventilation zones outboard of the core engine and failure will result in a large mass flow of relatively high temperature air escaping from the secondary air system; the design of the engine must accommodate this potential escape so that no component is over-pressurised or over-heated as a result. A novel device is presented that will limit the flow that escapes in the event of a pipe failure. This device has been developed from a number of flow elements from Fluidic technology applications. It has no moving parts and is thus suitable for use as a high-reliability failure protection device. The device consists of a Coanda diverter that can switch the flow through a vortex throttle so that the device has high and low resistance states. The diverter is conditioned to default to the low resistance state unless a control flow extracted from the device exceeds a critical value whereupon it will switch the device to a high resistance state. The level of the control flow is determined by the pressure ratio acting across the device. This is achieved by contrasting the flow characteristics of a metering orifice that determines the control flow with that of a diffuser fitted to the device outlet. The device has been shown to half the flow that escapes from a failed duct compared with an unrestricted duct of the same flow capacity. Experimental and numerical results are presented that show that the device is effective at the high pressure ratios pertaining to gas turbine operation. With suitable modification the device could be adapted to fulfill a number of other functions within a secondary air-system that require variation of flow resistance in response to a change in pressure ratio combined with the high reliability and robustness of a no-moving-parts device.

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Chidambaram, P., S. Mohd Ali, R. D. Tewari, C. Tan, A. H. Mazeli, D. P. Das, P. K. Tiwari, and A. Widyanita. "Dynamic-Geomechanics Coupled Modelling Helps Improve Understanding of the Reservoir and Improve Storage Capacity Estimate of Depleted Carbonate Gas Reservoir for Bulk Carbon Dioxide Sequestration." In SPE Offshore Europe Conference & Exhibition. SPE, 2023. http://dx.doi.org/10.2118/215579-ms.

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Abstract A depleted gas reservoir in Central Luconia field, located offshore Sarawak, was evaluated for future carbon dioxide (CO2) storage. This carbonate reservoir has experienced seafloor subsidence during producing life. When coupled dynamic-geomechanics model was history matched, it was discovered that earlier understanding of reservoir performance along with aquifer extent and size were incomplete. This new understanding has led to a significant change in forecasted CO2 storage capacity of the reservoir. In this reservoir, as production rate declined, reservoir pressure decline started reversing. During the producing life of the reservoir, standalone history matched dynamic model was used to forecast reservoir performance. This model sufficiently explained production performance and in fact production forecasts made from the model were reliable. After the reservoir had ceased to produce, it was evaluated for CO2 storage. As part of the CO2 storage studies, a coupled dynamic-geomechanics model was built. This was when it was noted that seafloor continued to subside even as reservoir pressure was increasing post cessation of production. This highlighted the fact that something other than hydrocarbon reservoir section was compacting. Further studies revealed that regional aquifer that was not included in the standalone dynamic model was undergoing compaction post-production. This reservoir has a bottom acting aquifer, which has a barrier/baffle zone at the bottom of the aquifer that separates it from an extended/regional aquifer. Standalone dynamic model was truncated at the barrier/baffle zone. This aquifer was sufficient to explain the pressure support received but was insufficient to explain sea floor subsidence post-production. Further studies revealed that the hydrocarbon section was in communication with extended aquifer. And the baffle zone has a major role to play in understanding CO2 storage. Using dynamic-geomechanics coupled model with extended aquifer, it was discovered that baffle zone undergoes pore collapse during production. This translates to significantly lower aquifer efflux across the baffle zone during CO2 injection compared to aquifer influx during production. This directly impacts the storage capacity of the reservoir since the invaded aquifer could not be efficiently displaced by injected CO2. Storage capacity estimate from coupled dynamic-geomechanics model is about 50% lower compared to standalone dynamic model.

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Ito, Miu, and Yuichi Sugai. "Evaluation of the Potential of Foam Producing Microorganism Improving Heterogeneity of Permeability for Novel Microbial Foam EOR." In SPE Asia Pacific Oil & Gas Conference and Exhibition. SPE, 2022. http://dx.doi.org/10.2118/210696-ms.

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Abstract The foam improves heterogeneity of permeability in oil reservoir and contributes to enhancing oil recovery. Both surfactant and gas are alternatingly injected into oil reservoir in foam EOR, therefore, it has several challenges: high cost of surfactant, formation of precipitation with bivalent cations, adsorption of surfactant on reservoir rock, etc. This study proposes the microbial foam EOR which overcomes those challenges by having microorganism generate foam in-situ. We have found an ability of a microorganism belonging to Pseudomonas aeruginosa to generate foam under anaerobic conditions. This study investigated the source materials constructing the foam and capacity of the foam to improve the heterogeneity of the permeability. The challenges of our study are the reproducibility of the foam generation and the foam stability. This study therefore examined the source materials of the foam to understand the mechanisms of the foam generation. We focused on protein, which has been suggested as a possible component of the foam in our previous studies, and examined the relationship between the amount of foam generated by P. aeruginosa and the concentration of protein in its culture solution. As a result, a positive correlation was found between them. This result indicates that the foam generated by P. aeruginosa is composed of the protein produced by the microorganism. Next, the performance of the foam decreasing permeability of high permeability porous media was evaluated through sand pack flooding experiment. P. aeruginosa was injected into a sand pack and cultivated in-situ. The post-flush water was injected into the sand pack after three days’ in-situ cultivation to measure the permeability. As a result, the permeability of the sand pack was successfully decreased to half after the cultivation. The permeability of a sand pack in which P. aeruginosa was injected with culture medium and in-situ cultivated was successfully decreased to half of initial. The efflux of bacterial cells of P. aeruginosa was detected after injecting 1.3 pore volumes of postflush water, which shows that the postflush water flowed through areas other than the area where P. aeruginosa grew and produced the foam. These results indicate that the foam produced in-situ by P. aeruginosa is effective for improving the heterogeneity of permeability in oil reservoir. This EOR can be operated at low cost without expensive chemicals. Because the foam produced by P. aeruginosa is induced by proteins, the precipitation will not be formed in oil reservoir. The stability of protein-induced foam is higher than that of surfactant-induced foam in the presence of oil or high saline conditions. The microbial foam EOR therefore has high potential improving the heterogeneity of permeability in oil reservoir more effectively than the conventional foam EOR.

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Звіти організацій з теми "Efflux Capacity"

Cheng, Wenke, Julia Boettner, Tina Fischer-Schaepman, Sarah Werner, Angela Kricke, Holger Thiele, and Petra Buettner. High-density lipoprotein Cholesterol Efflux Capacity and the Risk of Cardiovascular Diseases: A Systematic Review and Meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, July 2021. http://dx.doi.org/10.37766/inplasy2021.7.0006.

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Blumwald, Eduardo, and Avi Sadka. Citric acid metabolism and mobilization in citrus fruit. United States Department of Agriculture, October 2007. http://dx.doi.org/10.32747/2007.7587732.bard.

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Accumulation of citric acid is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate citric acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Citrate is accumulated in the vacuole of the juice sac cell, a process that requires both metabolic changes and transport across cellular membranes, in particular, the mitochondrial and the vacuolar (tonoplast) membranes. Although the accumulation of citrate in the vacuoles of juice cells has been clearly demonstrated, the mechanisms for vacuolar citrate homeostasis and the components controlling citrate metabolism and transport are still unknown. Previous results in the PIs’ laboratories have indicated that the expression of a large number of a large number of proteins is enhanced during fruit development, and that the regulation of sugar and acid content in fruits is correlated with the differential expression of a large number of proteins that could play significant roles in fruit acid accumulation and/or regulation of acid content. The objectives of this proposal are: i) the characterization of transporters that mediate the transport of citrate and determine their role in uptake/retrieval in juice sac cells; ii) the study of citric acid metabolism, in particular the effect of arsenical compounds affecting citric acid levels and mobilization; and iii) the development of a citrus fruit proteomics platform to identify and characterize key processes associated with fruit development in general and sugar and acid accumulation in particular. The understanding of the cellular processes that determine the citrate content in citrus fruits will contribute to the development of tools aimed at the enhancement of citrus fruit quality. Our efforts resulted in the identification, cloning and characterization of CsCit1 (Citrus sinensis citrate transporter 1) from Navel oranges (Citrus sinesins cv Washington). Higher levels of CsCit1 transcripts were detected at later stages of fruit development that coincided with the decrease in the juice cell citrate concentrations (Shimada et al., 2006). Our functional analysis revealed that CsCit1 mediates the vacuolar efflux of citrate and that the CsCit1 operates as an electroneutral 1CitrateH2-/2H+ symporter. Our results supported the notion that it is the low permeable citrateH2 - the anion that establishes the buffer capacity of the fruit and determines its overall acidity. On the other hand, it is the more permeable form, CitrateH2-, which is being exported into the cytosol during maturation and controls the citrate catabolism in the juice cells. Our Mass-Spectrometry-based proteomics efforts (using MALDI-TOF-TOF and LC2- MS-MS) identified a large number of fruit juice sac cell proteins and established comparisons of protein synthesis patterns during fruit development. So far, we have identified over 1,500 fruit specific proteins that play roles in sugar metabolism, citric acid cycle, signaling, transport, processing, etc., and organized these proteins into 84 known biosynthetic pathways (Katz et al. 2007). This data is now being integrated in a public database and will serve as a valuable tool for the scientific community in general and fruit scientists in particular. Using molecular, biochemical and physiological approaches we have identified factors affecting the activity of aconitase, which catalyze the first step of citrate catabolism (Shlizerman et al., 2007). Iron limitation specifically reduced the activity of the cytosolic, but not the mitochondrial, aconitase, increasing the acid level in the fruit. Citramalate (a natural compound in the juice) also inhibits the activity of aconitase, and it plays a major role in acid accumulation during the first half of fruit development. On the other hand, arsenite induced increased levels of aconitase, decreasing fruit acidity. We have initiated studies aimed at the identification of the citramalate biosynthetic pathway and the role(s) of isopropylmalate synthase in this pathway. These studies, especially those involved aconitase inhibition by citramalate, are aimed at the development of tools to control fruit acidity, particularly in those cases where acid level declines below the desired threshold. Our work has significant implications both scientifically and practically and is directly aimed at the improvement of fruit quality through the improvement of existing pre- and post-harvest fruit treatments.

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