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2009 | 56 | 3 |

Tytuł artykułu

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

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
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.

Wydawca

-

Rocznik

Tom

56

Numer

3

Opis fizyczny

p.439-446,fig.,ref.

Twórcy

autor
  • Medical University of Gdansk, Debinki 7, paw.29, 80-211 Gdansk, Poland
autor
autor
autor

Bibliografia

  • Baldwin SA, Mackey JR, Cass CE, Young JD (1999) Nucleoside transporters: molecular biology and implications for therapeutic development. Mol Med Today 5: 216-224. 
  • Fredholm BB, Irenius E, Kull B, Schulte G (2001) Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. Biochem Pharmacol 61: 443-448. 
  • Gessi S, Varani K, Merighi S, Fogli E, Sacchetto V, Benini A, Leung E, MacLennan S, Borea PA (2007) Adenosine and lymphocyte regulation. Purinergic Signal 3: 109-116. 
  • Hasko G, Crostein B (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25: 33-39. 
  • Hasko G, Linden J, Cronstein B, Pacher P (2008) Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 7: 759-770. 
  • Hershfield MS (2005) New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency. Eur J Immunol 35: 25-30. 
  • Martin C, Leone M, Viviand X, Ayem ML, Guieu R (2000) High adenosine plasma concentration as a prognostic index for outcome in patients with septic shock. Crit Care Med 28: 3198-3202. 
  • Pastor-Anglada M, Casado FJ, Valdés R, Mato J, Garcia-Manteiga J, Molina M (2001) Complex regulation of nucleoside transporter expression in epithelial and immune system cells. Mol Membr Biol 18: 81-85. 
  • Pawelczyk T, Bizon D, Angielski S (1992) The distribution of enzymes involved in purine metabolism in rat kidney. Biochim Biophys Acta 1116: 309-314. 
  • Pawelczyk T, Podgorska M, Sakowicz M (2003a) The effect of insulin on expression level of nucleoside transporters in diabetic rats. Mol Pharmacol 63: 81-88. 
  • Pawelczyk T, Sakowicz M, Podgorska M, Szczepanska-Konkel M (2003b) Insulin induced expression of adenosine kinase gene in rat lymphocytes by signaling through the mitogen activated protein kinase pathway. Exp Cell Res 286: 152-163. 
  • Pawelczyk T, Sakowicz-Burkiewicz M, Kocbuch K, Szutowicz A (2005) Differential effect of insulin and elevated glucose level on adenosine handling in rat T lymphocytes. J Cell Biochem 96: 1296-1310. 
  • Podgorska M, Kocbuch K, Pawelczyk T (2005) Recent advances in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters. Acta Biochim Polon 52: 749-758. 
  • Podgorska M, Kocbuch K, Grden M, Szutowicz A, Pawelczyk T (2006) Reduced ability to release adenosine by diabetic rat cardiac fibroblasts due to altered expression of nucleoside transporters. J Physiol 576: 179-189. 
  • Sakowicz M, Szutowicz A, Pawelczyk T (2004) Insulin and glucose induced changes in expression level of nucleoside transporters and adenosine transport in rat T lymphocytes. Biochem Pharmacol 68: 1309-1320. 
  • Sakowicz M, Szutowicz A, Pawelczyk T (2005) Differential effect of insulin and elevated glucose level on adenosine transport in rat B lymphocytes. Int Immunol 17: 145-154. 
  • Sakowicz-Burkiewicz M, Kocbuch K, Grden M, Szutowicz A, Pawelczyk T (2006) Diabetes-induced decrease of adenosine kinase expression impairs the proliferation potential of diabetic rat T lymphocytes. Immunology 118: 402-412. 
  • Sperlágh B, Dóda M, Baranyi M, Haskó G (2000) Ischemic-like condition releases norepinephrine and purines from different sources in suppressed rat spleen strips. J Neuroimmunol 111: 45-54

Typ dokumentu

Bibliografia

Identyfikatory

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