Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice.
Myoglobin is a cytoplasmic hemoprotein that is restricted to cardiomyocytes and oxidative skeletal myofibers and facilitates oxygen delivery during periods of high metabolic demand. Myoglobin content in skeletal muscle increases in response to hypoxic conditions. However, we previously reported that myoglobin-null mice are viable and fertile. In the present study, we define important functional, cellular, and molecular compensatory adaptations in the absence of myoglobin. Mice without myoglobin manifest adaptations in skeletal muscle that include a fiber type transition (type I to type II in the soleus muscle), increased expression of the hypoxia-inducible transcription factors hypoxia-inducible factor (HIF)-1alpha and HIF-2 (endothelial PAS domain protein), stress proteins such as heat shock protein 27, and the angiogenic growth factor vascular endothelial growth factor (soleus muscle), as well as increased nitric oxide metabolism (extensor digitorum longus). The resulting changes in angiogenesis, nitric oxide metabolism, and vasomotor regulation are likely to account for preserved exercise capacity of animals lacking myoglobin. These results demonstrate that mammalian organisms are capable of a broad spectrum of adaptive responses that can compensate for a potentially serious defect in cellular oxygen transport.
Grange
R W
RW
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Meeson
A
A
Chin
E
E
Lau
K S
KS
Stull
J T
JT
Shelton
J M
JM
Williams
R S
RS
Garry
D J
DJ
D000222:Adaptation, Physiological; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D017931:DNA Primers; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D009211:Myoglobin / Q000235:genetics* / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D009211:Myoglobin; D006152:Cyclic GMP