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The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

Publication ,  Journal Article
Pecorella, SRH; Potter, JVF; Cherry, AD; Peacher, DF; Welty-Wolf, KE; Moon, RE; Piantadosi, CA; Suliman, HB
Published in: Am J Physiol Lung Cell Mol Physiol
October 15, 2015

The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity.

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Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

October 15, 2015

Volume

309

Issue

8

Start / End Page

L857 / L871

Location

United States

Related Subject Headings

  • Young Adult
  • Respiratory System
  • RNA, Messenger
  • Quadriceps Muscle
  • Oxygen Consumption
  • Muscle, Skeletal
  • Muscle Proteins
  • Mitochondria, Muscle
  • Microscopy, Electron, Transmission
  • Male
 

Citation

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Pecorella, S. R. H., Potter, J. V. F., Cherry, A. D., Peacher, D. F., Welty-Wolf, K. E., Moon, R. E., … Suliman, H. B. (2015). The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle. Am J Physiol Lung Cell Mol Physiol, 309(8), L857–L871. https://doi.org/10.1152/ajplung.00104.2015
Pecorella, Shelly R. H., Jennifer V. F. Potter, Anne D. Cherry, Dionne F. Peacher, Karen E. Welty-Wolf, Richard E. Moon, Claude A. Piantadosi, and Hagir B. Suliman. “The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.Am J Physiol Lung Cell Mol Physiol 309, no. 8 (October 15, 2015): L857–71. https://doi.org/10.1152/ajplung.00104.2015.
Pecorella SRH, Potter JVF, Cherry AD, Peacher DF, Welty-Wolf KE, Moon RE, et al. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L857–71.
Pecorella, Shelly R. H., et al. “The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.Am J Physiol Lung Cell Mol Physiol, vol. 309, no. 8, Oct. 2015, pp. L857–71. Pubmed, doi:10.1152/ajplung.00104.2015.
Pecorella SRH, Potter JVF, Cherry AD, Peacher DF, Welty-Wolf KE, Moon RE, Piantadosi CA, Suliman HB. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L857–L871.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

October 15, 2015

Volume

309

Issue

8

Start / End Page

L857 / L871

Location

United States

Related Subject Headings

  • Young Adult
  • Respiratory System
  • RNA, Messenger
  • Quadriceps Muscle
  • Oxygen Consumption
  • Muscle, Skeletal
  • Muscle Proteins
  • Mitochondria, Muscle
  • Microscopy, Electron, Transmission
  • Male