Effect of Escherichia coli Endotoxin on Ascorbic Acid Transport in Isolated Adrenocortical Cells

Garcı́a, R.; Municio, A.M.

doi:10.3181/00379727-193-43036

Cited by 8 publications

(5 citation statements)

References 6 publications

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“…4), consistent with impaired reabsorption by the renal tubules of septic animals. Endotoxin and complement inhibit the active transport system responsible for concentrative uptake of ascorbate into cells (14,29), and this may contribute to the increased concentration of ascorbate in the urine of septic animals.…”

Section: Discussionmentioning

confidence: 99%

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

Armour

Tyml

Lidington

et al. 2001

Journal of Applied Physiology

121

147

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Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 +/- 4 to 29 +/- 2 microM) in plasma ascorbate concentration, 1,000% increase (from 46 +/- 13 to 450 +/- 93 microM) in urine ascorbate concentration, 20% decrease (from 115 +/- 2 to 91 +/- 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 +/- 1 to 17 +/- 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 microM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.

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Section: Discussionmentioning

confidence: 99%

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

Armour

Tyml

Lidington

et al. 2001

Journal of Applied Physiology

121

147

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“…The basic structure of LPS (lipid A) suggests that LPS aggregates alone or as complexes with plasma proteins such as albumin or lipoproteins may be efficient ligands for SR-BI. Supportive evidence for this possibility comes from the observation that organs highly expressing Cla-1 are targeted by 125 I-LPS⅐HDL complexes, and the accumulation of LPS in the adrenal glands has been suggested to induce adrenal cortical insufficiency (40,41) or hemorrhage in septic patients (17,19).…”

Section: Fig 6 Effect Of Cla-1 Overexpression On Bodipy-lps Uptake mentioning

confidence: 99%

“…Lipoprotein-free LPS strongly competes with HDL and exchangeable lipid-poor HDL apolipoproteins for HDL-binding sites in RAW cells that highly express SR-BI (40). Whereas LPS binding was measured on ice and in the absence of plasma factors facilitating LPS exchange, conditions highly unfavorable for HDL-LPS complex formation, the possibility of an effect of a small amount of HDL-associated LPS on HDL binding cannot be excluded.…”

Section: Fig 6 Effect Of Cla-1 Overexpression On Bodipy-lps Uptake mentioning

confidence: 99%

Binding and Internalization of Lipopolysaccharide by Cla-1, a Human Orthologue of Rodent Scavenger Receptor B1

Vishnyakova

Bocharov

Baranova

et al. 2003

Journal of Biological Chemistry

138

133

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Scavenger receptor, class B, type I (SR-BI) mediates selective uptake of high density lipoprotein (HDL) cholesteryl ester. SR-BI recognizes HDL, low density lipoprotein (LDL), exchangeable apolipoproteins, and protein-free lipid vesicles containing negatively charged phospholipids. Lipopolysaccharides (LPS) are highly glycosylated anionic phospholipids contributing to septic shock. Despite significant structural similarities between anionic phospholipids and LPS, the role of SR-BI in LPS uptake is unknown. Cla-1, the human SR-BI orthologue, was determined to be a LPSbinding protein and endocytic receptor mediating the binding and internalization of lipoprotein-free, monomerized LPS. LPS strongly competed with HDL, lipidfree apoA-I and apoA-II for HDL binding to the mouse RAW cells. Stably transfected HeLa cells expressing Cla-1-bound LPS with a K d of about 16 g/ml, and had a 3-4-fold increase in binding capacity and LPS uptake. Bodipy-labeled LPS uptake was found to initially accumulate in the plasma membrane and subsequently in a perinuclear region identified predominantly as the Golgi complex. Bodipy-LPS and Alexa-apoA-I had staining that colocalized on the cell surface and intracellularly indicating similar transport mechanisms. When associated with HDL, LPS uptake was increased in Cla-1 overexpressing HeLa cells by 5-10-fold. Cla-1-associated 3 H-LPS uptake exceeded 125 I-apolipoprotein uptake by 5-fold indicating a selective LPS uptake. Upon interacting with Cla-1 overexpressing HeLa cells, the complex (Bodipy-LPS/Alexa 488 apolipoprotein-labeled HDL) bound and was internalized as a holoparticle. Intracellularly, LPS and apolipoproteins were sorted to different intracellular compartments. With LPS-associated HDL, intracellular LPS colocalized predominantly with transferrin, indicating delivery to an endocytic recycling compartment. Our study reveals a close similarity between Cla-1-mediated selective LPS uptake and the recently described selective lipid sorting by rodent SR-BI. In summary, Cla-1 was found to bind and internalize monomerized and HDL-associated LPS, indicating that Cla-1 may play important role in septic shock by affecting LPS cellular uptake and clearance.Sepsis results from bacteria and their products entering the bloodstream and causing an overwhelming inflammatory response. Bacterial infections, as well as antibiotic therapy, cause the release of bacterial cell wall components including endotoxin (lipopolysaccharide (LPS), 1 lipoteichoic acid and peptidogycan (1); see Refs. 2 for review). Sepsis because of a Gramnegative bacterium is classically associated with endotoxemia, an acute phase reaction, and high mortality because of disseminated intravascular coagulation, multiple organ failure, and shock (3). LPS induces a broad spectrum of biological effects associated with the activation of immune and inflammatory cells, such as macrophages, monocytes, and endothelial cells. Systemic LPS-related activation of macrophages leads to overproduction of inflammatory mediators, such as leukocyte ...

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“…The presence of Na seems to decrease the Michaelis constant (Km) and, therefore, increase the affinity of the vitamin for its membrane carrier protein rather than changing the maximum velocity Vma; (Diliberto et al 1983;Padh & Aleo, 1987;Wilson & Dixon, 1989b). There is also some evidence that divalent metal ions, such as calcium, may also stimulate ascorbate transport (Padh & Aleo, 1987;Garcia & Municio, 1990;Washko et al 1990). …”

Section: Mechanisms Of Vitamin C Transportmentioning

confidence: 99%

The transport of vitamin C and effects of disease

Schorah

1992

Proc. Nutr. Soc.

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It has been known for a number of years that high concentrations of vitamin C (ascorbic acid + dehydroascorbic acid) occur in some cells, but it is only recently that we have begun to discover how high the levels are and also that the vitamin seems to be secreted onto epithelial surfaces (Table 1). If we assume that such concentrations and secretions are needed for the appropriate biological activity of the vitamin, it follows that transport of vitamin C will be required in order to sustain normal metabolic functions. Further, if transport is central to the metabolism of vitamin C, any defect in the process could lead to the development of disease.

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Effect of Escherichia coli Endotoxin on Ascorbic Acid Transport in Isolated Adrenocortical Cells

Cited by 8 publications

References 6 publications

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

Binding and Internalization of Lipopolysaccharide by Cla-1, a Human Orthologue of Rodent Scavenger Receptor B1

The transport of vitamin C and effects of disease

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