Skip to main content

Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells.

Publication ,  Journal Article
Hagen, SA; Kondyra, AL; Grocott, HP; El Moalem, H; Bainbridge, D; Mathew, JP; Newman, MF; Reves, JG; Schwinn, DA; Kwatra, MM
Published in: Anesthesiology
February 2003

BACKGROUND: Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation. METHODS: Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively. RESULTS: Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients. CONCLUSIONS: The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.

Duke Scholars

Published In

Anesthesiology

ISSN

0003-3022

Publication Date

February 2003

Volume

98

Issue

2

Start / End Page

343 / 348

Location

united states

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Substance P
  • Protein Serine-Threonine Kinases
  • Monocytes
  • Middle Aged
  • Male
  • Interleukin-8
  • Interleukin-6
  • Humans
  • G-Protein-Coupled Receptor Kinases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hagen, S. A., Kondyra, A. L., Grocott, H. P., El Moalem, H., Bainbridge, D., Mathew, J. P., … Kwatra, M. M. (2003). Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells. Anesthesiology, 98(2), 343–348.
Hagen, S. A., A. L. Kondyra, H. P. Grocott, H. El Moalem, D. Bainbridge, J. P. Mathew, M. F. Newman, J. G. Reves, D. A. Schwinn, and M. M. Kwatra. “Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells.Anesthesiology 98, no. 2 (February 2003): 343–48.
Hagen SA, Kondyra AL, Grocott HP, El Moalem H, Bainbridge D, Mathew JP, et al. Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells. Anesthesiology. 2003 Feb;98(2):343–8.
Hagen SA, Kondyra AL, Grocott HP, El Moalem H, Bainbridge D, Mathew JP, Newman MF, Reves JG, Schwinn DA, Kwatra MM. Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells. Anesthesiology. 2003 Feb;98(2):343–348.

Published In

Anesthesiology

ISSN

0003-3022

Publication Date

February 2003

Volume

98

Issue

2

Start / End Page

343 / 348

Location

united states

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Substance P
  • Protein Serine-Threonine Kinases
  • Monocytes
  • Middle Aged
  • Male
  • Interleukin-8
  • Interleukin-6
  • Humans
  • G-Protein-Coupled Receptor Kinases