Protein kinase C mediated high glucose effect on adenosine receptors expression in rat B lymphocytes.
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 A(1)-AR, A(2B)-AR, and A(3)-AR, but had no effect on the expression of A(2)A-AR. A selective inhibitor of Ca(2+)-dependent protein kinase C (PKC) isoforms suppressed the high glucose effect on A(1)-AR expression. Inhibition of PKC-delta with rottlerin blocked the high glucose effect on A(1)-AR mRNA level. An inhibitor of Raf-1 kinase completely blocked the high glucose effect on A(2B)-AR expression. The suppression of A(1)-AR and A(2B)-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 A(1)-AR, A(2B)-AR, and A(3)-AR in rat B lymphocytes.
Sakowicz-Burkiewicz
M
M
Department of Molecular Medicine, Medical University of Gdansk, Poland.
Kocbuch
K
K
Grden
M
M
Szutowicz
A
A
Pawelczyk
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis*
D047428:Protein Kinase Inhibitors; D018047:Receptors, Purinergic P1; D011493:Protein Kinase C; D005947:Glucose