Tissue factor-dependent pathway is not involved in exercise-induced formation of thrombin and fibrin.
In healthy individuals, prolonged intensive physical exercise leads to an activation of blood coagulation that results in the formation of thrombin and fibrin. This study investigated whether oxidative stress during intensive physical exercise induces tissue factor (TF) via activation of the redox-responsive transcription factor nuclear factor-kappaB (NF-kappaB). Twelve young men performed a standardized 1-h maximal run on a treadmill that gave rise to significant increases of markers of thrombin and fibrin formation. The ratio of intracellular reduced to oxidized glutathione as measured by HPLC decreased from 23.3 +/- 10.7 to 14.2 +/- 6.5 (P < 0.05), indicating the generation of free radicals during exercise. Electrophoretic mobility shift assays from nuclear extracts of peripheral blood mononuclear cells revealed that exercise testing increased NF-kappaB (p50/p65) binding activity to a NF-kappaB consensus sequence by 105 +/- 68% (P < 0.01) but did not affect NF-kappaB (p65/c-Rel) binding to a nonconsensus-kappaB-like site present in the TF promoter. Consistently, there was no exercise-induced increase in TF expression as demonstrated by TF-specific immunofluorescence staining and ELISA. Thus selective activation of NF-kappaB (p50/p65) during intensive physical exercise does not result in the expression of TF, suggesting that the TF-dependent pathway in peripheral blood mononuclear cells does not account for exercise-induced formation of thrombin and fibrin.
Weiss
Claus
C
Department of Internal Medicine VII/Sportsmedicine, University Hospital, 69115 Heidelberg, Germany. claus_weiss@med.uni-heidelberg.de
Bierhaus
Angelika
A
Kinscherf
Ralf
R
Hack
Volker
V
Luther
Thomas
T
Nawroth
Peter Paul
PP
Bärtsch
Peter
P
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005167:Factor VII / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000096:biosynthesis / Q000502:physiology*
D016328:NF-kappa B; D012333:RNA, Messenger; D005167:Factor VII; D005337:Fibrin; D013925:Thromboplastin; D013917:Thrombin; D005978:Glutathione