CoChat
Sign Up
Cited by 250

The DOI matches its Crossref record.

Hsp72 preserves muscle function and slows progression of severe muscular dystrophy

Gehrig, Stefan M., van der Poel, Chris, Sayer, Timothy A., Schertzer, Jonathan D., Henstridge, Darren C., Church, Jarrod E., Lamon, Severine, Russell, Aaron P., Davies, Kay E., Febbraio, Mark A., Lynch, Gordon S.·2012·Nature
DOI 10.1038/nature10980
Open this paper in CoChat — free account

Abstract

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatme…

Overview

Integrity signals

Registry

Crossref · 10.1038/nature10980

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Pharmacological induction of the heat-shock protein Hsp72 preserves muscle function and delays progression of dystrophic pathology in mouse models of muscular dystrophy.

    “Pharmacological induction of the heat-shock protein Hsp72 preserves muscle function and delays progression of dystrophic pathology in mouse models of muscular dystrophy (Gehrig et al., 2012).”

    From The Hallmarks of Aging (2013) · cites this paper as Gehrig et al., 2012

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 44

  1. Emery, A. E. The muscular dystrophies. Lancet 359, 687–695 (2002) · DOI · Paper page
  2. Ervasti, J. M. & Campbell, K. P. Membrane organization of the dystrophin–glycoprotein complex. Cell 66, 1121–1131 (1991) · DOI
  3. Koenig, M., Monaco, A. P. & Kunkel, L. M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53, 219–228 (1988) · DOI
  4. Blake, D. J., Weir, A., Newey, S. E. & Davies, K. E. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol. Rev. 82, 291–329 (2002) · DOI
  5. Straub, V., Rafael, J. A., Chamberlain, J. S. & Campbell, K. P. Animal models for muscular dystrophy show different patterns of sarcolemmal disruption. J. Cell Biol. 139, 375–385 (1997) · DOI · Paper page
  6. Turner, P. R., Westwood, T., Regen, C. M. & Steinhardt, R. A. Increased protein degradation results from elevated free calcium levels found in muscle from mdx mice. Nature 335, 735–738 (1988) · DOI
  7. Grady, R. M. et al. Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell 90, 729–738 (1997) · DOI
  8. Deconinck, A. E. et al. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 90, 717–727 (1997) · DOI · Paper page
  9. Gervasio, O. L., Whitehead, N. P., Yeung, E. W., Phillips, W. D. & Allen, D. G. TRPC1 binds to caveolin-3 and is regulated by Src kinase—role in Duchenne muscular dystrophy. J. Cell Sci. 121, 2246–2255 (2008) · DOI
  10. Fong, P. Y., Turner, P. R., Denetclaw, W. F. & Steinhardt, R. A. Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin. Science 250, 673–676 (1990) · DOI
  11. Bellinger, A. M. et al. Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nature Med. 15, 325–330 (2009) · DOI
  12. Nicolas-Metral, V., Raddatz, E., Kucera, P. & Ruegg, U. T. Mdx myotubes have normal excitability but show reduced contraction–relaxation dynamics. J. Muscle Res. Cell Motil. 22, 69–75 (2001) · DOI
  13. Tutdibi, O., Brinkmeier, H., Rudel, R. & Fohr, K. J. Increased calcium entry into dystrophin-deficient muscle fibres of MDX and ADR-MDX mice is reduced by ion channel blockers. J. Physiol. (Lond.) 515, 859–868 (1999) · DOI
  14. Goonasekera, S. A. et al. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J. Clin. Invest. 121, 1044–1052 (2011) · DOI
  15. Morine, K. J., Sleeper, M. M., Barton, E. R. & Sweeney, H. L. Overexpression of SERCA1a in the mdx diaphragm reduces susceptibility to contraction-induced damage. Hum. Gene Ther. 12, 1735–1739 (2010) · DOI
  16. Porter, J. D. et al. A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum. Mol. Genet. 11, 263–272 (2002) · DOI
  17. Acharyya, S. et al. Interplay of IKK/NF-κB signaling in macrophages and myofibres promotes muscle degeneration in Duchenne muscular dystrophy. J. Clin. Invest. 117, 889–901 (2007) · DOI
  18. Kolodziejczyk, S. M. et al. Activation of JNK1 contributes to dystrophic muscle pathogenesis. Curr. Biol. 11, 1278–1282 (2001) · DOI
  19. Monici, M. C., Aguennouz, M., Mazzeo, A., Messina, C. & Vita, G. Activation of nuclear factor-κB in inflammatory myopathies and Duchenne muscular dystrophy. Neurology 60, 993–997 (2003) · DOI
  20. Senf, S. M., Dodd, S. L., McClung, J. M. & Judge, A. R. Hsp70 overexpression inhibits NF-κB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy. FASEB J. 22, 3836–3845 (2008) · DOI
  21. Park, H. S., Lee, J. S., Huh, S. H., Seo, J. S. & Choi, E. J. Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J. 20, 446–456 (2001) · DOI
  22. Chung, J. et al. HSP72 protects against obesity-induced insulin resistance. Proc. Natl Acad. Sci. USA 105, 1739–1744 (2008) · DOI · Paper page
  23. Tupling, A. R. et al. HSP70 binds to the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA1a) and prevents thermal inactivation. J. Biol. Chem. 279, 52382–52389 (2004) · DOI
  24. Bornman, L., Polla, B. S., Lotz, B. P. & Gericke, G. S. Expression of heat-shock/stress proteins in Duchenne muscular dystrophy. Muscle Nerve 18, 23–31 (1995) · DOI
  25. Lou, J. S., Weiss, M. D. & Carter, G. T. Assessment and management of fatigue in neuromuscular disease. Am. J. Hosp. Palliat. Care 27, 145–157 (2010) · DOI
  26. Finsterer, J. Cardiopulmonary support in Duchenne muscular dystrophy. Lung 184, 205–215 (2006) · DOI
  27. Stedman, H. H. et al. The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352, 536–539 (1991) · DOI
  28. Briguet, A., Courdier-Fruh, I., Foster, M., Meier, T. & Magyar, J. P. Histological parameters for the quantitative assessment of muscular dystrophy in the mdx-mouse. Neuromuscul. Disord. 14, 675–682 (2004) · DOI
  29. Literati-Nagy, B. et al. Improvement of insulin sensitivity by a novel drug, BGP-15, in insulin-resistant patients: a proof of concept randomized double-blind clinical trial. Horm. Metab. Res. 41, 374–380 (2009) · DOI
  30. Morimoto, R. I. Cells in stress: transcriptional activation of heat shock genes. Science 259, 1409–1410 (1993) · DOI
  31. Marber, M. S. et al. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J. Clin. Invest. 95, 1446–1456 (1995) · DOI
  32. Taleb, M. et al. Hsp70 inhibits aminoglycoside-induced hair cell death and is necessary for the protective effect of heat shock. J. Assoc. Res. Otolaryngol. 9, 277–289 (2008) · DOI
  33. Literati-Nagy, B. et al. Beneficial effect of the insulin sensitizer (HSP inducer) BGP-15 on olanzapine-induced metabolic disorders. Brain Res. Bull. 20, 340–344 (2010) · DOI
  34. Saegusa, Y. & Tabata, H. Usefulness of infrared thermometry in determining body temperature in mice. J. Vet. Med. Sci. 65, 1365–1367 (2003) · DOI
  35. Gregorevic, P., Plant, D. R., Leeding, K. S., Bach, L. A. & Lynch, G. S. Improved contractile function of the mdx dystrophic mouse diaphragm muscle after insulin-like growth factor-I administration. Am. J. Pathol. 161, 2263–2272 (2002) · DOI
  36. Schertzer, J. D., Ryall, J. G. & Lynch, G. S. Systemic administration of IGF-I enhances oxidative status and reduces contraction-induced injury in skeletal muscles of mdx dystrophic mice. Am. J. Physiol. 291, 499–505 (2006)
  37. Schertzer, J. D., Gehrig, S. M., Ryall, J. G. & Lynch, G. S. Modulation of insulin-like growth factor (IGF)-I and IGF-binding protein interactions enhances skeletal muscle regeneration and ameliorates the dystrophic pathology in mdx mice. Am. J. Pathol. 171, 1180–1188 (2007) · DOI
  38. Gehrig, S. M., Koopman, R., Naim, T., Tjoakarfa, C. & Lynch, G. S. Making fast-twitch dystrophic muscles bigger protects them from contraction injury and attenuates the dystrophic pathology. Am. J. Pathol. 176, 29–33 (2010) · DOI
  39. Briguet, A., Courdier-Fruh, I., Foster, M., Meier, T. & Magyar, J. P. Histological parameters for the quantitative assessment of muscular dystrophy in the mdx-mouse. Neuromuscul. Disord. 14, 675–682 (2004) · DOI
  40. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976) · DOI · Paper page
  41. Schertzer, J. D. et al. β2-Agonist administration increases sarcoplasmic reticulum Ca2+-ATPase activity in aged rat skeletal muscle. Am. J. Physiol. 288, 526–533 (2005)
  42. Plant, D. R. & Lynch, G. S. Depolarization-induced contraction and SR function in mechanically skinned muscle fibres from dystrophic mdx mice. Am. J. Physiol. 285, C522–C528 (2003) · DOI
  43. Murphy, K. T. et al. Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function. FASEB J. 24, 4433–4442 (2010) · DOI
  44. Green, M. C. A rapid method for clearing and staining specimens for the demonstration of bone. Ohio J. Sci. 52, 31–33 (1952)

Cited by

Sorted by citations

Metadata

Authors
Gehrig, S. M., van der Poel, C., Sayer, T. A., Schertzer, J. D., Henstridge, D. C., Church, J. E., Lamon, S., Russell, A. P., Davies, K. E., Febbraio, M. A., & Lynch, G. S.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2012-04
Volume
484
Issue
7394
Pages
394-398
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature10980
Cited by
250
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review