Advertisement

Cell Stress and Chaperones

, Volume 18, Issue 5, pp 675–681 | Cite as

Isolated hearts treated with skeletal muscle homogenates exhibit altered function

  • Alex P. Di Battista
  • Marius LockeEmail author
Short Communication

Abstract

Skeletal muscle fiber damage and necrosis can result in the release of intracellular molecules into the extracellular environment. These molecules, termed damage-associated molecular patterns (DAMPs), can act as signals capable of initiating immune and/or inflammatory responses through interactions with pattern recognition receptors. To investigate whether skeletal muscle DAMPs interact with the heart and alter cardiac function, isolated rat hearts were perfused for 75 min with buffer containing 1 μg/ml of either soleus (slow), white gastrocnemius (WG, fast), or heat-stressed white gastrocnemius (HSWG) skeletal muscle homogenates. Left ventricular developed pressure (LVDP) and rates of pressure increase/decrease (±dP/dt) were measured using the Langendorff technique. Compared to controls, no changes in LVDP or +dP/dt were observed over the 75-min perfusion when homogenates from the WG muscles were added. In contrast, at 30 min and thereafter, a decreased LVDP and +dP/dt was observed in the hearts treated with soleus muscle homogenates. The hearts treated with HSWG homogenates also showed a decrease in LVDP from 45 min until the end of perfusion. These results suggest that molecules present in slow muscle and heat-stressed muscle are capable of altering cardiac function. Thus, muscle fiber type and/or heat shock protein content of skeletal muscles may be factors that influence cardiac function following skeletal muscle damage.

Keywords

Skeletal Muscle Fiber Left Ventricular Develop Pressure Muscle Homogenate White Gastrocnemius Follow Heat Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Asea A (2008) Heat shock proteins and Toll-like receptors. In: Toll-like receptors (TLRs) and innate immunity. Springer, Berlin, pp 111–127Google Scholar
  2. Asea A, Kraeft SK, Kurt-Jones EA et al (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442PubMedCrossRefGoogle Scholar
  3. Benjamin IJ, McMillan DR (1998) Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res 83:117–132PubMedCrossRefGoogle Scholar
  4. Chen H, Wu Y, Zhang Y et al (2006) Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination. FEBS Lett 580:3145–3152PubMedCrossRefGoogle Scholar
  5. Douglas PS, O’Toole ML, Hiller WD et al (1987) Cardiac fatigue after prolonged exercise. Circulation 76:1206–1213PubMedCrossRefGoogle Scholar
  6. Draisma A, Bemelmans R, van der Hoeven JG et al (2009) Microcirculation and vascular reactivity during endotoxemia and endotoxin tolerance in humans. Shock 31:581–585PubMedCrossRefGoogle Scholar
  7. Febbraio MA, Ott P, Nielsen HB et al (2002) Exercise induces hepatosplanchnic release of heat shock protein 72 in humans. J Physiol 544:957–962PubMedCrossRefGoogle Scholar
  8. Fehrenbach E, Niess AM, Voelker K et al (2005) Exercise intensity and duration affect blood soluble HSP72. Int J Sports Med 26:552–557PubMedCrossRefGoogle Scholar
  9. Fitts RH (1994) Cellular mechanisms of muscle fatigue. Physiol Rev 74:49–94PubMedCrossRefGoogle Scholar
  10. Frier BC, Noble EG, Locke M (2008) Diabetes-induced atrophy is associated with a muscle-specific alteration in NF-kappaB activation and expression. Cell Stress Chaperones 13:287–296PubMedCrossRefGoogle Scholar
  11. Halliwill JR (2001) Mechanisms and clinical implications of post-exercise hypotension in humans. Exerc Sport Sci Rev 29:65–70PubMedCrossRefGoogle Scholar
  12. Hingorani AD, Cross J, Kharbanda RK et al (2000) Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 102:994–999PubMedCrossRefGoogle Scholar
  13. Kim S-C, Stice JP, Chen L et al (2009) Extracellular heat shock protein 60, cardiac myocytes, and apoptosis. Circ Res 105:1186–1195PubMedCrossRefGoogle Scholar
  14. Komulainen J, Vihko V (1994) Exercise-induced necrotic muscle damage and enzyme release in the four days following prolonged submaximal running in rats. Pflugers Arch - Eur J Physiol 428:346–351CrossRefGoogle Scholar
  15. La Gerche A, Connelly KA, Mooney DJ et al (2008) Biochemical and functional abnormalities of left and right ventricular function after ultra-endurance exercise. Heart 94:860–866PubMedCrossRefGoogle Scholar
  16. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRefGoogle Scholar
  17. Latchman DS (2001) Heat shock proteins and cardiac protection. Cardiovasc Res 51:637–646PubMedCrossRefGoogle Scholar
  18. Lieber RL, Fridén J (1999) Mechanisms of muscle injury after eccentric contraction. J Sci Med Sport 2:253–265PubMedCrossRefGoogle Scholar
  19. Locke M (2000) Heat shock transcription factor activation and Hsp72 accumulation in aged skeletal muscle. Cell Stress Chaperones 5:45–51PubMedCrossRefGoogle Scholar
  20. Locke M, Noble EG, Atkinson BG (1991) Inducible isoform of HSP70 is constitutively expressed in a muscle fiber type specific pattern. Am J Physiol 261:C774–C779PubMedGoogle Scholar
  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  22. MacDonald JR, MacDougall JD, Hogben CD (2000) The effects of exercise duration on post-exercise hypotension. J Hum Hypertens 14:125–129PubMedCrossRefGoogle Scholar
  23. Manson J, Thiemermann C, Brohi K (2012) Trauma alarmins as activators of damage-induced inflammation. Br J Surg 99(Suppl 1):12–20PubMedCrossRefGoogle Scholar
  24. Mathur S, Walley KR, Wang Y et al (2011) Extracellular heat shock protein 70 induces cardiomyocyte inflammation and contractile dysfunction via TLR2. Circ J 75:2445–2452PubMedCrossRefGoogle Scholar
  25. Middleton N, Shave R, George K et al (2006) Left ventricular function immediately following prolonged exercise: a meta-analysis. Med Sci Sports Exerc 38:681–687PubMedCrossRefGoogle Scholar
  26. Neilan TG, Yoerger DM, Douglas PS et al (2006) Persistent and reversible cardiac dysfunction among amateur marathon runners. Eur Hear J 27:1079–1084CrossRefGoogle Scholar
  27. Neufer PD, Ordway GA, Hand GA et al (1996) Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle. Am J Physiol 271:C1828–C1837PubMedGoogle Scholar
  28. Rubartelli A, Lotze MT (2007) Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox. Trends Immunol 28:429–436PubMedCrossRefGoogle Scholar
  29. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521PubMedCrossRefGoogle Scholar
  30. Staron RS, Hikida RS, Hagerman FC et al (1984) Human skeletal muscle fiber type adaptability to various workloads. J Histochem Cytochem 32:146–152PubMedCrossRefGoogle Scholar
  31. Steensberg A, van Hall G, Osada T et al (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529(Pt 1):237–242PubMedCrossRefGoogle Scholar
  32. Steensberg A, Keller C, Starkie RL et al (2002) IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 283:E1272–E1278PubMedGoogle Scholar
  33. Stoecklein VM, Osuka A, Lederer JA (2012) Trauma equals danger—damage control by the immune system. J Leukoc Biol 92:539–551PubMedCrossRefGoogle Scholar
  34. Tiidus PD (2008) Skeletal muscle damage and repair. Human Kinetics, ChampaignGoogle Scholar
  35. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350PubMedCrossRefGoogle Scholar
  36. Vabulas RM, Ahmad-Nejad P, Ghose S et al (2002) HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 277:15107–15112PubMedCrossRefGoogle Scholar
  37. Walsh RC, Koukoulas I, Garnham A et al (2001) Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 6:386–393PubMedCrossRefGoogle Scholar
  38. Zhang Q, Raoof M, Chen Y et al (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–107PubMedCrossRefGoogle Scholar
  39. Zou N, Ao L, Cleveland JC et al (2008) Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion. Am J Physiol Heart Circ Physiol 294:H2805–H2813PubMedCrossRefGoogle Scholar

Copyright information

© Cell Stress Society International 2013

Authors and Affiliations

  1. 1.Faculty of Kinesiology and Physical EducationUniversity of TorontoTorontoCanada

Personalised recommendations