Transcription in response to physical stress--clues to the molecular mechanisms of exercise-induced asthma.
To clarify stress-induced immunological reactions and molecular events during exercise and the potential relevance to exercise-induced bronchoconstriction, transcriptional responses to standardized physical stress were determined. Six healthy, young volunteers underwent an endurance exercise of 90% of their individual anaerobic threshold for 90 min. Time-dependent alterations in the expression pattern of leukocytes from healthy, trained subjects were analyzed by DNA microarrays before and 2 h and 6 h after exercise. Starting out from a large collection of cDNA library clones comprising more than 70,000 human expressed sequence tags, we selected, designed, and immobilized oligonucleotide probes (60-70mers) for transcripts of 5000 stress- and inflammation-relevant genes. Exercise-induced stress provoked changes in the expression of 433 gene activities 2 h and/or 6 h after exercise, which could be grouped into six clusters. The most prominent feature was an enhanced transcription of two genes, coding for 5-lipoxygenase (ALOX5) and ALOX5-activating protein. Moreover, enhanced levels of leukotriene B4 (LTB4) and LTC4 (P<0.05) were detected in plasma after exercise. Our data demonstrate that exercise alters the activities of a distinct number of genes. In particular, they possibly provide novel insights into the molecular mechanisms of exercise-induced bronchoconstriction and suggest that enhanced transcription of ALOX5 and its activating protein together with a present predisposition of the subject critically contribute to exercise-induced asthma.
Hilberg
Thomas
T
Department of Sports Medicine Friedrich-Schiller-University Jena, Germany. thomas.hilberg@uni-jena.de
Deigner
Hans-Peter
HP
Möller
Eva
E
Claus
Ralf A
RA
Ruryk
Andriy
A
Gläser
Doreen
D
Landre
Julien
J
Brunkhorst
Frank M
FM
Reinhart
Konrad
K
Gabriel
Holger H W
HH
Russwurm
Stefan
S
D058927:5-Lipoxygenase-Activating Proteins; D000328:Adult; D001250:Asthma, Exercise-Induced / Q000209:etiology* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D007975:Leukotriene B4 / Q000096:biosynthesis; D017997:Leukotriene C4 / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013312:Stress, Physiological / Q000378:metabolism*; D014158:Transcription, Genetic
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D015850:Interleukin-6; D008565:Membrane Proteins; D007975:Leukotriene B4; D017997:Leukotriene C4