Functional correlation between the Ser/Thr-phosphorylation of band-3 and band-3-mediated transmembrane anion transport in human erythrocytes

Baggio, Bruno; Bordin, Luciana; Clari, Giulio; Gambaro, Giovanni; Moret, V.

doi:10.1016/0005-2736(93)90173-w

Cited by 26 publications

(20 citation statements)

References 26 publications

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“…Okadaic acid readily enters cells, and numerous studies have demonstrated that it enhances the phosphorylation of many cellular proteins (23,24), presumably by preventing dephosphorylation. In this report, we showed that okadaic acid significantly increased the phosphorylation level of mOAT and this phosphorylation paralleled in time and concentration the decrease of basolateral PAH transport activity.…”

Section: Discussionmentioning

confidence: 99%

Regulation of mOAT-mediated Organic Anion Transport by Okadaic Acid and Protein Kinase C in LLC-PK1 Cells

You¹,

Kuze²,

Kohanski³

et al. 2000

Journal of Biological Chemistry

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Organic anion transporters in the kidney proximal tubule play an essential role in eliminating a wide range of organic anions including endogenous compounds, xenobiotics, and their metabolites, thereby preventing their potentially toxic effects within the body. We have previously cloned a cDNA encoding an organic anion transporter from mouse kidney (mOAT) (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J. G., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478; Kuze, K., Graves, P., Leahy, A., Wilson, P., Stuhlmann, H., and You, G. (1999) J. Biol. Chem. 274, 1519 -1524). In the present study, we assessed the potential for regulation of this transporter by heterologous expression of mOAT in the pig proximal tubule-like cell line, LLC-PK 1 . We report here that both protein phosphatase (PP1/PP2A) inhibitor, okadaic acid, and protein kinase C (PKC) activators down-regulate mOAT-mediated transport of para-aminohippuric acid (PAH), a prototypic organic anion, in a time-and concentrationdependent manner. However their mechanisms of action for this down-regulation are distinct. Okadaic acid modulated PAH transport, at least in part, through phosphorylation/dephosphorylation of mOAT; phosphoamino acid analysis indicated this phosphorylation occurs on serine. In contrast, PKC activation induced a decrease in the maximum transport velocity (V max ) of PAH transport without direct phosphorylation of the transporter protein. Together these results provide the first demonstration that regulation of organic anion transport by mOAT is likely to be tightly controlled directly and indirectly by phosphatase PP1/PP2A and PKC. Our results also suggest that kinases other than PKC are involved in this process.Renal organic anion transport plays a vital role in the elimination of a wide variety of potentially toxic and negatively charged waste products of metabolism, drugs, environmental pollutants, and their metabolites from the body. The transport mechanisms responsible for this elimination have been extensively studied (3-5). Based on these studies, it has been suggested that the transport of organic anions is a complex process involving distinctly different proteins at the apical and basolateral membranes of the proximal tubule cells. Organic anions are transported across the basolateral membrane into the cell in exchange for intracellular dicarboxylates, which are subsequently returned into the cell via a sodium-dependent dicarboxylate transporter. Once inside the cell, organic anions are subject to intracellular binding and sequestration within vesicular structures. Finally, luminal exit is thought to occur by anion exchange and/or facilitated diffusion (3-5).We (1, 2) and others (6 -11) have recently cloned the organic anion transporter cDNA from kidneys of multiple species. Using computer modeling based on hydropathy analysis, the predicted proteins share several common features, including 12 putative membrane-spanning segments, a cluster of potential glycosylation sites located in the first extracellular...

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Section: Discussionmentioning

confidence: 99%

Regulation of mOAT-mediated Organic Anion Transport by Okadaic Acid and Protein Kinase C in LLC-PK1 Cells

You¹,

Kuze²,

Kohanski³

et al. 2000

Journal of Biological Chemistry

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“…Three dietary oils, namely fish, coconut, and soybean oil, were studied. Ingestion of soybean oil, rich in O-6FAs, led to an increase in plasma levels of n-6 AA and higher rates of urinary excretion of calcium and oxalate [9][10][11][12][13][14]. The exogenous n-6 AA are incorporated into the membranes of erythrocytes.…”

Section: Kidney Stonesmentioning

confidence: 99%

“…The exogenous n-6 AA are incorporated into the membranes of erythrocytes. This results in a boost in the phosphorylation level of band-3 and related band-3 proteins, which in turn mediate oxalate transport [11,15]. These biochemical pathways occur in renal tubular cells (along with erythrocytes).…”

Section: Kidney Stonesmentioning

confidence: 99%

Influence of polyunsaturated fatty acids on urologic inflammation

et al. 2015

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“…90 On the other hand, in a parallel study it was shown that intestinal oxalate uptake is not modulated by protein kinase C, but by different protein kinases, in particular by Ca 2+ -calmodulin kinase. 90 On the other hand, in a parallel study it was shown that intestinal oxalate uptake is not modulated by protein kinase C, but by different protein kinases, in particular by Ca 2+ -calmodulin kinase.…”

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confidence: 99%

Pathogenesis of Idiopathic Calcium Nephrolithiasis: Update 1997

Baggio

Plebani

Gambaro

1998

Critical Reviews in Clinical Laboratory Sciences

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Idiopathic calcium nephrolithiasis (ICN) is a frequent disease in Western countries. The physicochemical theory of lithogenesis, which explains stone formation by the precipitation, growth, and crystalline aggregation of lithogenic salts in the urine, has contributed greatly to the understanding of the pathogenesis of calcium urolithiasis. However, several aspects are still unexplained; the co-existence of familial occurrence, primary tubular dysfunctions with ICN, and anomalies in the systemic handling of oxalate and calcium led to the development of a cellular hypothesis of ICN. A number of cellular defects in the handling of ions has been reported that involves both anion and cation transport. These anomalies are probably the expression of a still unknown cellular defect in idiopathic calcium stone formers. We suggested that an anomaly in the cell membrane composition might be responsible for the complex array of cell ion flux abnormalities observed in ICN. Recently, a disorder in the n-6 polyunsaturated fatty acid series has been described; it is characterized by a lower linoleic acid content and a higher arachidonic acid concentration in both plasma and erythrocyte membrane phospholipids of renal calcium stone patients. This anomaly could cause an increased activity of ion carriers; furthermore, it may lead to increased prostaglandin synthesis and to secondary phenomena at the kidney, skeletal, and intestinal level. As a consequence, critical conditions for lithogenesis in the kidney may ensue. The data suggest a common pathogenesis for hypercalciuria and hyperoxaluria. The systemic defect in the phospholipid arachidonic acid level may be both of dietary or genetic origin; experimental data suggest that the increase in delta-6 desaturase activity, the limiting enzyme in the metabolic pathway of polyunsaturated fatty acids, might be relevant to the pathogenesis of lipid abnormalities observed in nephrolithiasis and to the pathogenesis of ICN and its related problems (at the kidney, intestinal, and bone level).

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Functional correlation between the Ser/Thr-phosphorylation of band-3 and band-3-mediated transmembrane anion transport in human erythrocytes

Cited by 26 publications

References 26 publications

Regulation of mOAT-mediated Organic Anion Transport by Okadaic Acid and Protein Kinase C in LLC-PK1 Cells

Regulation of mOAT-mediated Organic Anion Transport by Okadaic Acid and Protein Kinase C in LLC-PK1 Cells

Influence of polyunsaturated fatty acids on urologic inflammation

Pathogenesis of Idiopathic Calcium Nephrolithiasis: Update 1997

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