User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Adenosine inhibits protein synthesis in isolated rat hepatocytes. Evidence for a lack of involvement of intracellular calcium in the mechanism of inhibition.

Primary tabs

Tinton, S A Chow, S C Buc Calderon, Pedro [UCL] Kass, G E Orrenius, S

Extracellularly added adenosine and ATP are potent inhibitors of protein synthesis in liver cells. In this study, the possible involvement of Ca2+ in the mechanism of inhibition of protein synthesis by adenosine was investigated. Stimulation of freshly isolated hepatocytes with adenosine or ATP, at concentrations that impaired protein synthesis, induced an increase in the cytosolic free Ca2+ concentration ([Ca2+]i). However, there was no correlation between the increase in [Ca2+]i and inhibition of radiolabelled leucine incorporation into proteins. Thus, the stimulation of hepatocytes with the V1-receptor agonist, vasopressin, or with the nucleotide triphosphates, UTP and GTP, elicited changes in [Ca2+]i similar to those observed after ATP or adenosine addition, but did not affect protein synthesis. ATP produced near complete discharge of Ca2+ from the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in isolated hepatocytes, whereas adenosine only had a partial effect. Depletion of the hormone-sensitive Ca2+ pool by adenosine was transient. In contrast, prolonged depletion of internal Ca2+ by thapsigargin resulted in the inhibition of protein synthesis in hepatocytes. However, the inhibition of radiolabelled leucine incorporation into proteins by thapsigargin was further augmented by the additional presence of adenosine. These results show that the inhibition of protein synthesis by adenosine in isolated hepatocytes is not mediated by an increase in [Ca2+]i or depletion of internal pool(s) sensitive to inositol 1,4,5-trisphosphate or thapsigargin.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Publication date 1995
Journal information "European journal of biochemistry / FEBS" - Vol. 229, no. 2, p. 419-25 (1995)
Peer reviewed yes
issn 0014-2956
Publication status Publié
Affiliation UCL
MESH Subject Adenosine - pharmacology ; Adenosine Triphosphate - analogs & derivatives - pharmacology ; Animals ; Calcium - metabolism ; Calcium-Transporting ATPases - antagonists & inhibitors ; Liver - metabolism ; Male ; Nucleotides - pharmacology ; Protein Biosynthesis ; Rats ; Rats, Wistar ; Terpenes - pharmacology ; Thapsigargin ; Vasopressins - pharmacology
Links
  1. Berridge Michael J., Inositol trisphosphate and calcium signalling, 10.1038/361315a0
  2. Brostrom C. O., Mol. Pharmacol., 29, 104 (1985)
  3. Chin K. V., Int. J. Biochem., 20, 1313 (1988)
  4. Brostrom C., Calcium-Dependent Regulation Of Protein Synthesis In Intact Mammalian Cells, 10.1146/annurev.physiol.52.1.577
  5. Kimball S. R., Am. J. Physiol, 263, E958 (1992)
  6. Preston S. F., Cell Calcium, 13, 303 (1992)
  7. Wong W L, Brostrom M A, Kuznetsov G, Gmitter-Yellen D, Brostrom C O, Inhibition of protein synthesis and early protein processing by thapsigargin in cultured cells, 10.1042/bj2890071
  8. Lodish H. F., J. Biol. Chem., 263, 2107 (1988)
  9. Pfefter S., Annu. Rev. Biochem., 56, 829 (1987)
  10. Carafoli E, Intracellular Calcium Homeostasis, 10.1146/annurev.biochem.56.1.395
  11. Kimball S. R., J. Biol. Chem., 265, 16794 (1990)
  12. Kimball S. R., J. Biochem. Biophys. Res. Commun., 177, 1082 (1991)
  13. Taylor Colin W., Richardson Alan, Structure and function of inositol triphosphate receptors, 10.1016/0163-7258(91)90043-l
  14. Gill D. L., Adv. Second Messenger Phosphoprotein Res., 26, 265 (1992)
  15. Kass G. E. N., J. Biol. Chem., 264, 15192 (1989)
  16. Thastrup O., Proc. Natl Acad. Sci., 87, 2466 (1990)
  17. Llopis J, Chow S B, Kass G E N, Gahm A, Orrenius S, Comparison between the effects of the microsomal Ca2+-translocase inhibitors thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone on cellular calcium fluxes, 10.1042/bj2770553
  18. Tinton Sandrine A., Lefebvre Véronique H., Cousin Olivier C., Buc-Calderon Pedro M., Cytolytic effects and biochemical changes induced by extracellular ATP to isolated hepatocytes, 10.1016/0167-4889(93)90169-p
  19. Charest R., J. Biol. Chem., 260, 15789 (1985)
  20. Keppens S., The complex interaction of ATP and UTP with isolated hepatocytes. How many receptors?, 10.1016/0306-3623(93)90304-g
  21. Moatassim C., Biochim. Biophys. Acta, 1134, 31 (1992)
  22. Díaz Antonio, Guinzberg Raquel, Uribe Salvador, Piña Enrique, Metabolic responses of isolated hepatocytes to adenosine; Dependence on external calcium, 10.1016/0024-3205(91)90067-l
  23. Sistare F. D., J. Biol. Chem., 260, 12744 (1985)
  24. Guinzberg R., Diazcruz A., Uribe S., Pina E., Inhibition of Adenosine-Mediated Responses in Isolated Hepatocytes by Depolarizing Concentrations of K+, 10.1006/bbrc.1993.2465
  25. Kass G E, Webb D L, Chow S C, Llopis J, Berggren P O, Receptor-mediated Mn2+influx in rat hepatocytes: comparison of cells loaded with Fura-2 ester and cells microinjected with Fura-2 salt, 10.1042/bj3020005
  26. Llopis J, Kass G E N, Gahm A, Orrenius S, Evidence for two pathways of receptor-mediated Ca2+entry in hepatocytes, 10.1042/bj2840243
  27. Grynkiewicz G., J. Biol. Chem., 260, 3440 (1985)
  28. Chow S. C., Lipids, 24, 700 (1989)
  29. Lowry O. H., J. Biol. Chem., 193, 265 (1951)
  30. Keppens S, De Wulf H, P2-purinergic control of liver glycogenolysis, 10.1042/bj2310797
  31. Staddon J. M., Eur. J. Biochem., 151, 567 (1985)
  32. Carabaza A., J. Biol. Chem., 265, 2724 (1990)
  33. Koike M, Kashiwagura T, Takeguchi N, Gluconeogenesis stimulated by extracellular ATP is triggered by the initial increase in the intracellular Ca2+concentration of the periphery of hepatocytes, 10.1042/bj2830265
  34. Ghosh T. K., J. Biol. Chem., 266, 24690 (1991)
  35. Llopis J., Biochem. Pharmacol., 45, 2209 (1993)
  36. Allan C J, Exton J H, Quantification of inositol phospholipid breakdown in isolated rat hepatocytes, 10.1042/bj2900865
  37. Haussinger D., Eur. J. Biochem., 169, 645 (1987)
  38. Nagelkerke J F, Dogterom P, De Bont H J G M, Mulder G J, Prolonged high intracellular free calcium concentrations induced by ATP are not immediately cytotoxic in isolated rat hepatocytes. Changes in biochemical parameters implicated in cell toxicity, 10.1042/bj2630347
  39. Bartrons R, Van Schaftingen E, Hers H G, The ability of adenosine to decrease the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. A cyclic AMP-mediated effect, 10.1042/bj2180157
  40. Buxton D B, Robertson S M, Olson M S, Stimulation of glycogenolysis by adenine nucleotides in the perfused rat liver, 10.1042/bj2370773
  41. John Hoffer L., Lowenstein John M., Effects of adenosine and adenosine analogues on glycogen metabolism in isolated rat hepatocytes, 10.1016/0006-2952(86)90775-6
  42. Abbrachio M. P., Drug Development Res., 28, 207 (1993)
  43. Collis Michael G., Hourani Susanna M.O., Adenosine receptor subtypes, 10.1016/0165-6147(93)90094-z
  44. Carruthers A. M., Trends Pharmacol. Sci., 14, 290 (1993)
  45. Burnstock G., Cell membrane receptors for drugs and hormones: a multidisciplinary approach, 107 (1978)
  46. Kennedy C., Arch. Int. Pharmacodyn., 303, 30 (1990)
  47. Lund P, Cornell N W, Krebs H A, Effect of adenosine on the adenine nucleotide content and metabolism of hepatocytes, 10.1042/bj1520593
  48. Fox I H, Kelley W N, The Role of Adenosine and 2'-Deoxyadenosine in Mammalian Cells, 10.1146/annurev.bi.47.070178.003255
  49. Marchand Jean-Claude, Lavoinne Alain, Giroz Monique, Matray François, The influence of adenosine on intermediary metabolism of isolated hepatocytes, 10.1016/s0300-9084(80)80286-0
  50. Hoffman D. R., J. Biol. Chem., 255, 10822 (1980)
  51. Ueland P. M., Pharmacol. Rev., 34, 223 (1982)
  52. Bontemps F., Proc. Natl Acad. Sci USA, 80, 2829 (1983)
  53. Bontemps F, Vincent M F, Van den Berghe G, Mechanisms of elevation of adenosine levels in anoxic hepatocytes, 10.1042/bj2900671
Bibliographic reference Tinton, S A ; Chow, S C ; Buc Calderon, Pedro ; Kass, G E ; Orrenius, S. Adenosine inhibits protein synthesis in isolated rat hepatocytes. Evidence for a lack of involvement of intracellular calcium in the mechanism of inhibition.. In: European journal of biochemistry / FEBS, Vol. 229, no. 2, p. 419-25 (1995)
Permanent URL http://hdl.handle.net/2078.1/11910