Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions

Carsten Lundby; Max Gassmann; Henriette Pilegaard

doi:10.1007/s00421-005-0085-5

Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions

Carsten Lundby, Max Gassmann, Henriette Pilegaard

Molecular Integrative Physiology

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

89 Citationer (Scopus)

Abstract

Udgivelsesdato: 2006-Mar

Originalsprog	Engelsk
Tidsskrift	European Journal of Applied Physiology
Vol/bind	96
Udgave nummer	4
Sider (fra-til)	363-9
Antal sider	6
ISSN	1439-6319
DOI	https://doi.org/10.1007/s00421-005-0085-5
Status	Udgivet - 2005

Bibliografisk note

Keywords: Adult; Basic Helix-Loop-Helix Transcription Factors; Exercise; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leg; Muscle, Skeletal; Physical Fitness; RNA, Messenger

Adgang til dokumentet

10.1007/s00421-005-0085-5

Citationsformater

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title = "Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions",

abstract = "Regular exercise induces a variety of adaptive responses that enhance the oxidative and metabolic capacity of human skeletal muscle. Although the physiological adjustments of regular exercise have been known for decades, the underlying mechanisms are still unclear. The hypoxia inducible factors 1 and 2 (HIFs) are clearly related heterodimeric transcription factors that consist of an oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon heterodimerization, HIFs induce the transcription of a variety of genes including erythropoietin (EPO), transferrin and its receptor, as well as vascular endothelial growth factor (VEGF) and its receptor. Considering that several of these genes are also induced with exercise, we tested the hypothesis that the mRNA level of HIF-1alpha and HIF-2alpha subunits increases with a single exercise bout, and that this response is blunted with training. We obtained muscle biopsies from a trained (5 days/week during 4 weeks) and untrained leg from the same human subject before, immediately after, and during the recovery from a 3 h two-legged knee extensor exercise bout, where the two legs exercised at the same absolute workload. In the untrained leg, the exercise bout induced an increase (P<0.05) in HIF-1alpha fold and HIF-2alpha fold mRNA at 6 h of recovery. In contrast, HIF-1alpha and HIF-2alpha mRNA levels were not altered at any time point in the trained leg. Obviously, HIF-1alpha and HIF-2alpha mRNA levels are transiently increased in untrained human skeletal muscle in response to an acute exercise bout, but this response is blunted after exercise training. We propose that HIFs expression is upregulated with exercise and that it may be an important transcription factor that regulates adaptive gene responses to exercise.",

author = "Carsten Lundby and Max Gassmann and Henriette Pilegaard",

note = "Keywords: Adult; Basic Helix-Loop-Helix Transcription Factors; Exercise; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leg; Muscle, Skeletal; Physical Fitness; RNA, Messenger",

year = "2005",

doi = "10.1007/s00421-005-0085-5",

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T1 - Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions

AU - Lundby, Carsten

AU - Gassmann, Max

AU - Pilegaard, Henriette

N1 - Keywords: Adult; Basic Helix-Loop-Helix Transcription Factors; Exercise; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leg; Muscle, Skeletal; Physical Fitness; RNA, Messenger

PY - 2005

Y1 - 2005

N2 - Regular exercise induces a variety of adaptive responses that enhance the oxidative and metabolic capacity of human skeletal muscle. Although the physiological adjustments of regular exercise have been known for decades, the underlying mechanisms are still unclear. The hypoxia inducible factors 1 and 2 (HIFs) are clearly related heterodimeric transcription factors that consist of an oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon heterodimerization, HIFs induce the transcription of a variety of genes including erythropoietin (EPO), transferrin and its receptor, as well as vascular endothelial growth factor (VEGF) and its receptor. Considering that several of these genes are also induced with exercise, we tested the hypothesis that the mRNA level of HIF-1alpha and HIF-2alpha subunits increases with a single exercise bout, and that this response is blunted with training. We obtained muscle biopsies from a trained (5 days/week during 4 weeks) and untrained leg from the same human subject before, immediately after, and during the recovery from a 3 h two-legged knee extensor exercise bout, where the two legs exercised at the same absolute workload. In the untrained leg, the exercise bout induced an increase (P<0.05) in HIF-1alpha fold and HIF-2alpha fold mRNA at 6 h of recovery. In contrast, HIF-1alpha and HIF-2alpha mRNA levels were not altered at any time point in the trained leg. Obviously, HIF-1alpha and HIF-2alpha mRNA levels are transiently increased in untrained human skeletal muscle in response to an acute exercise bout, but this response is blunted after exercise training. We propose that HIFs expression is upregulated with exercise and that it may be an important transcription factor that regulates adaptive gene responses to exercise.

AB - Regular exercise induces a variety of adaptive responses that enhance the oxidative and metabolic capacity of human skeletal muscle. Although the physiological adjustments of regular exercise have been known for decades, the underlying mechanisms are still unclear. The hypoxia inducible factors 1 and 2 (HIFs) are clearly related heterodimeric transcription factors that consist of an oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon heterodimerization, HIFs induce the transcription of a variety of genes including erythropoietin (EPO), transferrin and its receptor, as well as vascular endothelial growth factor (VEGF) and its receptor. Considering that several of these genes are also induced with exercise, we tested the hypothesis that the mRNA level of HIF-1alpha and HIF-2alpha subunits increases with a single exercise bout, and that this response is blunted with training. We obtained muscle biopsies from a trained (5 days/week during 4 weeks) and untrained leg from the same human subject before, immediately after, and during the recovery from a 3 h two-legged knee extensor exercise bout, where the two legs exercised at the same absolute workload. In the untrained leg, the exercise bout induced an increase (P<0.05) in HIF-1alpha fold and HIF-2alpha fold mRNA at 6 h of recovery. In contrast, HIF-1alpha and HIF-2alpha mRNA levels were not altered at any time point in the trained leg. Obviously, HIF-1alpha and HIF-2alpha mRNA levels are transiently increased in untrained human skeletal muscle in response to an acute exercise bout, but this response is blunted after exercise training. We propose that HIFs expression is upregulated with exercise and that it may be an important transcription factor that regulates adaptive gene responses to exercise.

U2 - 10.1007/s00421-005-0085-5

DO - 10.1007/s00421-005-0085-5

M3 - Journal article

C2 - 16284786

SN - 1439-6319

VL - 96

SP - 363

EP - 369

JO - European Journal of Applied Physiology

JF - European Journal of Applied Physiology

IS - 4

ER -