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Protein kinase C mediated high glucose effect on adenosine receptors expression in rat B lymphocytes

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

Journal of Physiology and Pharmacology

2009

tom 60

nr 3

145-153

Hyperglycemia-induced alterations of adenosine receptors (ARs) expression are implicated in the pathomechanism leading to impaired function of the lymphocytes in diabetes. However, the signaling pathways utilized by glucose to regulate ARs expression are unknown. This work was undertaken to investigate the impact of high glucose level on the ARs expression in rat B lymphocytes. The results presented in this report demonstrate that rat B lymphocytes express all four types of ARs at the mRNA and protein level. Exposing B cells to high glucose (25 mM) suppressed the expression of A1-AR, A2B-AR, and A3-AR, but had no effect on the expression of A2A-AR. A selective inhibitor of Ca2+-dependent protein kinase C (PKC) isoforms suppressed the high glucose effect on A3-AR expression. Inhibition of PKC- with rottlerin blocked the high glucose effect on A1-AR mRNA level. An inhibitor of Raf-1 kinase completely blocked the high glucose effect on A2B-AR expression. The suppression of A1-AR and A2B-AR mRNA expression induced by high glucose was blocked by an inhibitor (PD98059) of MAPK kinase (MEK). In conclusion, high glucose utilizes a signaling pathway involving some elements of the MAPK pathway and different PKC isoforms to suppress the expression of A1-AR, A2B-AR, and A3-AR in rat B lymphocytes.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Grden M.

1 Kocbuch K.

1 Pawelczyk T.

1 Sakowicz-Burkiewicz M.

1 Szutowicz A.

1 2009

Wyniki wyszukiwania

Protein kinase C mediated high glucose effect on adenosine receptors expression in rat B lymphocytes