Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

TY - JOUR

T1 - Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

AU - Mounier, Rémi

AU - Pedersen, Bente Klarlund

AU - Plomgaard, Peter

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Skeletal muscle is well known to exhibit a high degree of plasticity depending on environmental changes, such as various oxygen concentrations. Studies of the oxygen-sensitive subunit α of hypoxia-inducible factor-1 (HIF-1) are difficult owing to the large variety of functionally diverse muscle fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1α mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1α mRNA and protein owing to their higher oxidative capacity. We have shown, in normoxic conditions, a higher HIF-1α protein expression in predominantly oxidative muscles than in predominantly glycolytic muscles. However, the HIF-1α mRNA expression pattern was not in agreement with the HIF-1α protein level. Interestingly, none of the HIF-1α target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented a significantly higher VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1α and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described here, support a key role for HIF-1α for maintaining muscle homeostasis in non-hypoxic conditions.

AB - Skeletal muscle is well known to exhibit a high degree of plasticity depending on environmental changes, such as various oxygen concentrations. Studies of the oxygen-sensitive subunit α of hypoxia-inducible factor-1 (HIF-1) are difficult owing to the large variety of functionally diverse muscle fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1α mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1α mRNA and protein owing to their higher oxidative capacity. We have shown, in normoxic conditions, a higher HIF-1α protein expression in predominantly oxidative muscles than in predominantly glycolytic muscles. However, the HIF-1α mRNA expression pattern was not in agreement with the HIF-1α protein level. Interestingly, none of the HIF-1α target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented a significantly higher VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1α and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described here, support a key role for HIF-1α for maintaining muscle homeostasis in non-hypoxic conditions.

KW - Adult

KW - Anoxia

KW - Gene Expression

KW - Humans

KW - Hypoxia-Inducible Factor 1, alpha Subunit

KW - Male

KW - Muscle Fibers, Fast-Twitch

KW - Muscle Fibers, Slow-Twitch

KW - RNA, Messenger

KW - Vascular Endothelial Growth Factor A

U2 - 10.1113/expphysiol.2010.052928

DO - 10.1113/expphysiol.2010.052928

M3 - Journal article

C2 - 20494919

SN - 0958-0670

VL - 95

SP - 899

EP - 907

JO - Experimental Physiology

JF - Experimental Physiology

IS - 8

ER -