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Recent advances in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters

100%

Podgorska M., Kocbuch K., Pawelczyk T.

Acta Biochimica Polonica

2005

vol. 52

issue 4

749-758

Nucleoside transporters (NT) facilitate the movement of nucleosides and nucleobases across cell membranes. NT-mediated transport is vital for the synthesis of nucleic acids in cells that lack de novo purine synthesis. Some nucleosides display biological activity and act as signalling molecules. For example, adenosine exerts a potent action on many physiological processes including vasodilatation, hormone and neurotransmitter release, platelet aggregation, and lipolysis. Therefore, carrier-mediated transport of this nucleoside plays an important role in modulating cell function, because the efficiency of the transport processes determines adenosine availability to its receptors or to metabolizing enzymes. Nucleoside transporters are also key elements in anticancer and antiviral therapy with the use of nucleoside analogues. Mammalian cells possess two major nucleoside transporter families: equilibrative (ENT) and concentrative (CNT) Na+-dependent ones. This review characterizes gene loci, substrate specificity, tissue distribution, membrane topology and structure of ENT and CNT proteins. Regulation of nucleoside transporters by various factors is also presented.

Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes

88%

Kocbuch K., Sakowicz-Burkiewicz M., Grden M., Szutowicz A., Pawelczyk T.

Acta Biochimica Polonica

2009

vol. 56

issue 3

439-446

In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10-8 M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10-11 M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10-8 M insulin comparing to cells grown in 10-11 M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

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2 Acta Biochimica Polonica

1 2009

1 2005

2 Kocbuch K.

2 Pawelczyk T.

1 Grden M.

1 Podgorska M.

1 Sakowicz-Burkiewicz M.

1 Szutowicz A.

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Recent advances in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters

Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes