A mechanism converting psychosocial stress into mononuclear cell activation
Top Cited Papers
- 10 February 2003
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (4) , 1920-1925
- https://doi.org/10.1073/pnas.0438019100
Abstract
Little is known about the mechanisms converting psychosocial stress into cellular dysfunction. Various genes, up-regulated in atherosclerosis but also by psychosocial stress, are controlled by the transcription factor nuclear factor κB (NF-κB). Therefore, NF-κB is a good candidate to convert psychosocial stress into cellular activation. Volunteers were subjected to a brief laboratory stress test and NF-κB activity was determined in peripheral blood mononuclear cells (PBMC), as a window into the body and because PBMC play a role in diseases such as atherosclerosis. In 17 of 19 volunteers, NF-κB was rapidly induced during stress exposure, in parallel with elevated levels of catecholamines and cortisol, and returned to basal levels within 60 min. To model this response, mice transgenic for a strictly NF-κB-controlled β-globin transgene were stressed by immobilization. Immobilization resulted in increased β-globin expression, which could be reduced in the presence of the α1-adrenergic inhibitor prazosin. To define the role of adrenergic stimulation in the up-regulation of NF-κB, THP-1 cells were induced with physiological amounts of catecholamines for 10 min. Only noradrenaline resulted in a dose- and time-dependent induction of NF-κB and NF-κB-dependent gene expression, which depended on pertussis-toxin-sensitive G protein-mediated phosphophatidylinositol 3-kinase, Ras/Raf, and mitogen-activated protein kinase activation. Induction was reduced by α 1 - and β-adrenergic inhibitors. Thus, noradrenaline-dependent adrenergic stimulation results in activation of NF-κB in vitro and in vivo . Activation of NF-κB represents a downstream effector for the neuroendocrine response to stressful psychosocial events and links changes in the activity of the neuroendocrine axis to the cellular response.Keywords
This publication has 62 references indexed in Scilit:
- Allostatic load as a predictor of functional declineJournal of Clinical Epidemiology, 2002
- Noradrenaline-Induced Paxillin Phosphorylation, ERK Activation and MEK-Regulated Contraction in Intact Rat Mesenteric ArteriesJournal of Vascular Research, 2002
- MEK1/2–ERK1/2 Mediates α1-Adrenergic Receptor-stimulated Hypertrophy in Adult Rat Ventricular MyocytesJournal of Molecular and Cellular Cardiology, 2001
- α-Lipoic Acid: A Metabolic Antioxidant Which Regulates NF-κB Signal Transduction and Protects Against Oxidative InjuryDrug Metabolism Reviews, 1998
- Two alternative job stress models and the risk of coronary heart disease.American Journal of Public Health, 1998
- Psychosocial stress causes endothelial injury in cynomolgus monkeys via β1-adrenoceptor activationAtherosclerosis, 1998
- Antiatherogenic effects of β-adrenergic blocking agents: Theoretical, experimental, and epidemiologic considerationsPublished by Elsevier ,1994
- The ‘Trier Social Stress Test’ – A Tool for Investigating Psychobiological Stress Responses in a Laboratory SettingNeuropsychobiology, 1993
- Effect of Iraqi missile war on incidence of acute myocardial infarction and sudden death in Israeli civiliansThe Lancet, 1991
- Social Stress and Atherosclerosis in Normocholesterolemic MonkeysScience, 1983