Abstract
Muscle fiber-type changes in hypoxic conditions in accordance with pyruvate dehydrogenase kinase (Pdk)-1 and hypoxia inducible factor (Hif)-1α were investigated in rats. Hif-1α and its down-stream molecule Pdk-1 are well known for readily response to hypoxia. We questioned their roles in relation to changes in myosin heavy chain (MyHC) composition in skeletal muscles. We hypothesize that the level of Pdk-1 with respect to the level of Hif-1α determines MyHC composition of the muscle in rats in hypoxia. Young male rats were housed in a chamber maintained at 11.5% (for sustained hypoxia) or fluctuating between 11.5 and 20.8% (for intermittent hypoxia or IH) oxygen levels. Then, muscle tissues from the geniohyoid (GH), soleus, and anterior tibialis (TA) were obtained at the end of hypoxic conditionings. After both hypoxic conditionings, protein levels of Pdk-1 and Hif-1 increased in GH muscles. GH muscles in acute sustained hypoxia favor an anaerobic glycolytic pathway, resulting in an increase in glycolytic MyHC IIb protein-rich fibers while maintain original fatigue-resistant MyHC IIa protein in the fibers; thus, the numbers of IIa- and IIb MyHC co-expressing fibers increased. Exogenous Pdk-1 over-expression using plasmid vectors elevated not only the glycolytic MyHC IIb, but also IIx as well as IIa expressions in C2C12 myotubes in ambient air significantly. The increase of dual expression of IIa- and IIb MyHC proteins in fibers harvested from the geniohyoid muscle has a potential to improve endurance as shown in our fatigability tests. By increasing the Pdk-1/Hif-1 ratio, a mixed-type muscle could alter endurance within the innate characteristics of the muscle toward more fatigue resistant. We conclude that an increased Pdk-1 level in skeletal muscle helps maintain MyHC compositions to be a fatigue resistant mixed-type muscle.
Highlights
Increased fatigability of the tongue protruding muscles after intermittent hypoxia (IH) is associated with the pathophysiology of obstructive sleep apnea (OSA), one of the most prevalent global health problems (McSharry et al, 2012; Kim et al, 2014)
We suggest that a relative amount of PDK1 with respect to hypoxia inducible factor (Hif)-1 plays a significant role in the phenotypic composition of fiber types in a mixed-type muscle
Up to a 3.8fold (3.8 ± 0.37) increase of Hif-1α level was observed after intermittent hypoxic exposure in the predominantly glycolytic muscles TA, and a 7.4-fold (7.4 ± 1.70) increase was observed in the sustained hypoxia of TA muscles
Summary
Increased fatigability of the tongue protruding muscles after intermittent hypoxia (IH) is associated with the pathophysiology of obstructive sleep apnea (OSA), one of the most prevalent global health problems (McSharry et al, 2012; Kim et al, 2014). Roles of PDK-1 in Muscles from IIa abundant to IIb dominant in the geniohyoid (GH) muscle, and which is accompanied by an increased fatigability (McGuire et al, 2002; Pae et al, 2005). This change in tongue muscles may explain a part of the pathophysiology of OSA. We think this change is initiated with an increased level of ubiquitous oxygen sensing molecule, hypoxia inducible factor (Hif)-1α in the muscle. We assume that pyruvate dehydrogenase kinase (PDK) may play such a role linking metabolic cue to compositional phenotypic changes in the muscle leading to changes of functional properties of the muscle
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