title: PDGF-β receptor and PKC have no effect on angiotensin II-induced JAK2 and STAT1 phosphorylation in vascular smooth muscle cells under high glucose condition.
abstract: BACKGROUND
  The mechanisms responsible for the accelerated cardiovascular disease in diabetes, as well as the increased hypertrophic effects of angiotensin II (Ang II) under hyperglycemic condition, are not very clear. Evidences show that platelet-derived growth factor (PDGF) and protein kinase C (PKC) play a critical role in this effect. In our study, we examined the role of PKC and PDGF receptor on JAK2 and STAT1 phosphorylation under high glucose (HG) condition (25 mmol/L) in response to Ang II in cultured vascular smooth muscle cells (VSMC).
  
  
  METHODS
  VSMCs were isolated from the thoracic aorta of male Wistar rats and were cultured. Growth-arrested VSMCs were placed in either normal glucose (NG) or HG condition for 48 h and then VSMCs were stimulated with agonists and antagonists. The tyrosine phosphorylation of JAK2 or STAT were determined by immunoblotting using specific antibodies.
  
  
  RESULTS
  High glucose markedly increased the phosphorylation of tyrosine residues of JAK2 and serine residues of STAT 1 compared with cells cultured in NG (5.5 mmol/L) with and without Ang II stimulation. Experiments made with specific PDGF-β receptor inhibitor AG1295 and PKC inhibitor GF109203X showed that there were no changes in Ang II-stimulated JAK2 and STAT1 phosphorylation under NG and HG conditions compared with experiments without inhibitors.
  
  
  CONCLUSIONS
  According to our findings, Ang II-stimulated JAK2 and STAT1 phosphorylation under either NG or HG condition do not proceed via a different pathway rather than PKC and PDGF-β receptor.
authors.affiliation: Department of Biochemistry, Medical School, Mustafa Kemal University, Antakya, Hatay, Turkey. ozturk@mku.edu.tr
authors.forename: Oktay Hasan
authors.initials: OH
authors.lastname: Öztürk
authors.forename: Arzu
authors.initials: A
authors.lastname: Çetin
authors.forename: Alper
authors.initials: A
authors.lastname: Tokay
authors.forename: Fatih
authors.initials: F
authors.lastname: Uzuner
authors.forename: Gamze
authors.initials: G
authors.lastname: Tanrıöver
authors.forename: Akın
authors.initials: A
authors.lastname: Yeşilkaya
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000008:administration & dosage; D007211:Indoles / Q000737:chemistry; D053614:Janus Kinase 2 / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008301:Maleimides / Q000737:chemistry; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D020032:Tyrphostins / Q000737:chemistry
chemical_list: C407689:6,7-dimethoxy-2-phenylquinoxaline; D007211:Indoles; D008301:Maleimides; D050794:STAT1 Transcription Factor; D020032:Tyrphostins; D000804:Angiotensin II; D020797:Receptor, Platelet-Derived Growth Factor beta; D053614:Janus Kinase 2; D011493:Protein Kinase C; D005947:Glucose; C070515:bisindolylmaleimide I