Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice

Robert W. Grange, Annette Meeson, E. V A Chin, Kim S. Lau, James T. Stull, John M. Shelton, R. Sanders Williams, Daniel J. Garry

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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 myoglobinnull 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)-1α 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number5 50-5
StatePublished - 2001

Fingerprint

Myoglobin
Muscle
Skeletal Muscle
Metabolism
Nitric Oxide
HSP27 Heat-Shock Proteins
Oxygen
Hypoxia-Inducible Factor 1
Angiogenesis Inducing Agents
Heat-Shock Proteins
Cardiac Myocytes
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Animals
Transcription Factors
Proteins
Defects
Fibers

Keywords

  • Hypoxia
  • Oxygen metabolism
  • Transgenic mice
  • Vascularization

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Grange, R. W., Meeson, A., Chin, E. V. A., Lau, K. S., Stull, J. T., Shelton, J. M., ... Garry, D. J. (2001). Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice. American Journal of Physiology - Cell Physiology, 281(5 50-5).

Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice. / Grange, Robert W.; Meeson, Annette; Chin, E. V A; Lau, Kim S.; Stull, James T.; Shelton, John M.; Williams, R. Sanders; Garry, Daniel J.

In: American Journal of Physiology - Cell Physiology, Vol. 281, No. 5 50-5, 2001.

Research output: Contribution to journalArticle

Grange, RW, Meeson, A, Chin, EVA, Lau, KS, Stull, JT, Shelton, JM, Williams, RS & Garry, DJ 2001, 'Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice', American Journal of Physiology - Cell Physiology, vol. 281, no. 5 50-5.
Grange, Robert W. ; Meeson, Annette ; Chin, E. V A ; Lau, Kim S. ; Stull, James T. ; Shelton, John M. ; Williams, R. Sanders ; Garry, Daniel J. / Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice. In: American Journal of Physiology - Cell Physiology. 2001 ; Vol. 281, No. 5 50-5.
@article{266105b10ef74d8b94992724a27164e6,
title = "Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice",
abstract = "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 myoglobinnull 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)-1α 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.",
keywords = "Hypoxia, Oxygen metabolism, Transgenic mice, Vascularization",
author = "Grange, {Robert W.} and Annette Meeson and Chin, {E. V A} and Lau, {Kim S.} and Stull, {James T.} and Shelton, {John M.} and Williams, {R. Sanders} and Garry, {Daniel J.}",
year = "2001",
language = "English (US)",
volume = "281",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 50-5",

}

TY - JOUR

T1 - Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice

AU - Grange, Robert W.

AU - Meeson, Annette

AU - Chin, E. V A

AU - Lau, Kim S.

AU - Stull, James T.

AU - Shelton, John M.

AU - Williams, R. Sanders

AU - Garry, Daniel J.

PY - 2001

Y1 - 2001

N2 - 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 myoglobinnull 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)-1α 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.

AB - 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 myoglobinnull 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)-1α 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.

KW - Hypoxia

KW - Oxygen metabolism

KW - Transgenic mice

KW - Vascularization

UR - http://www.scopus.com/inward/record.url?scp=0035205239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035205239&partnerID=8YFLogxK

M3 - Article

C2 - 11600411

AN - SCOPUS:0035205239

VL - 281

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 50-5

ER -