Skip to main content
SpringerLink
Log in

Regulation of Mitochondrial Function by Hypoxia and Inflammation in Sepsis: A Putative Role for Hypoxia Inducible Factor

  • Conference paper
Yearbook of Intensive Care and Emergency Medicine

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 2008))

  • 1115 Accesses

Abstract

Sepsis-related organ failure is the leading cause of mortality in European intensive care units (ICU). Although the inflammatory cascade of mediators in response to infection is well known, the relationships between regional inflammation, microvascular heterogeneity, hypoxia and hypoxia-inducible gene expression, and finally, organ dysfunction, are unknown. Growing evidence suggests that not only low oxygen supply to the tissues secondary to macrovascular and microvascular alterations, but also altered cellular oxygen utilization is involved in the development of multiorgan dysfunction [1]–[3]. Microbial products and innate and adaptive dysregulated immune response to infection directly affect parenchymal cells of organs and may contribute to multiorgan dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kreymann G, Grosser S, Buggisch P, Gottschall C, Matthaei S, Greten H (1993) Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock. Crit Care Med 21:1012–1019

    Article  CAS  PubMed  Google Scholar 

  2. Boekstegers P, Weidenhofer S, Kapsner T, Werdan K (1994) Skeletal muscle partial pressure of oxygen in patients with sepsis. Crit Care Med 22:640–650

    Article  CAS  PubMed  Google Scholar 

  3. Hotchkiss RS, Swanson PE, Freeman BD, et al (1999) Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 27:1230–1251

    Article  CAS  PubMed  Google Scholar 

  4. Schatz G (1995) Mitochondria: beyond oxidative phosphorylation. Biochim Biophys Acta 1271:123–126

    PubMed  Google Scholar 

  5. Semenza GL (2007) Oxygen-dependent regulation of mitochondrial respiration by hypoxiainducible factor 1. Biochem J 405:1–9

    CAS  PubMed  Google Scholar 

  6. Ivan M, Kondo K, Yang H, et al (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–468

    Article  CAS  PubMed  Google Scholar 

  7. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002) Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295:858–861

    Article  CAS  PubMed  Google Scholar 

  8. Mansfield KD, Guzy RD, Pan Y, et al (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1:393–399

    Article  CAS  PubMed  Google Scholar 

  9. Schumacker PT (2005) Hypoxia-inducible factor-1 (HIF-1). Crit Care Med 33:S423–425

    Article  PubMed  Google Scholar 

  10. Cramer T, Yamanishi Y, Clausen BE, et al (2003) HIF-1alpha is essential for myeloid cellmediated inflammation. Cell 112:645–657

    Article  CAS  PubMed  Google Scholar 

  11. Kantrow SP, Taylor DE, Carraway MS, Piantadosi CA (1997) Oxidative metabolism in rat hepatocytes and mitochondria during sepsis. Arch Biochem Biophys 345:278–288

    Article  CAS  PubMed  Google Scholar 

  12. Unno N, Wang H, Menconi MJ, et al (1997) Inhibition of inducible nitric oxide synthase ameliorates endotoxin-induced gut mucosal barrier dysfunction in rats. Gastroenterology 113:1246–1257

    Article  CAS  PubMed  Google Scholar 

  13. Zingarelli B, Day BJ, Crapo JD, Salzman AL, Szabo C (1997) The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock. Br J Pharmacol 120:259–267

    Article  CAS  PubMed  Google Scholar 

  14. Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H (1986) Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 250:E634–640

    CAS  PubMed  Google Scholar 

  15. Vary TC (1991) Increased pyruvate dehydrogenase kinase activity in response to sepsis. Am J Physiol 260:E669–674

    CAS  PubMed  Google Scholar 

  16. Brealey D, Karyampudi S, Jacques TS, et al (2004) Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure. Am J Physiol Regul Integr Comp Physiol 286:R491–497

    CAS  PubMed  Google Scholar 

  17. Radi R, Rodriguez M, Castro L, Telleri R (1994) Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys 308:89–95

    Article  CAS  PubMed  Google Scholar 

  18. Szabo C (2007) Poly (ADP-ribose) polymerase activation and circulatory shock. Novartis Found Symp 280:92–103

    Article  CAS  PubMed  Google Scholar 

  19. Goldfarb RD, Marton A, Szabo E, et al (2002) Protective effect of a novel, potent inhibitor of poly(adenosine 5′-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis. Crit Care Med 30:974–980

    Article  CAS  PubMed  Google Scholar 

  20. Khan AU, Delude RL, Han YY, et al (2002) Liposomal NAD(+) prevents diminished O(2) consumption by immunostimulated Caco-2 cells. Am J Physiol Lung Cell Mol Physiol 282:L1082–1091

    CAS  PubMed  Google Scholar 

  21. Martin-Oliva D, Aguilar-Quesada R, O’Valle F, et al (2006) Inhibition of poly(ADP-ribose) polymerase modulates tumor-related gene expression, including hypoxia-inducible factor-1 activation, during skin carcinogenesis. Cancer Res 66:5744–5756

    Article  CAS  PubMed  Google Scholar 

  22. Crouser ED, Julian MW, Huff JE, Struck J, Cook CH (2006) Carbamoyl phosphate synthase-1: a marker of mitochondrial damage and depletion in the liver during sepsis. Crit Care Med 34:2439–2446

    Article  CAS  PubMed  Google Scholar 

  23. Blouin CC, Page EL, Soucy GM, Richard DE (2004) Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha. Blood 103:1124–1130

    Article  CAS  PubMed  Google Scholar 

  24. Frede S, Stockmann C, Freitag P, Fandrey J (2006) Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappaB. Biochem J 396:517–527

    Article  CAS  PubMed  Google Scholar 

  25. Kim HY, Kim YH, Nam BH, et al (2007) HIF-1alpha expression in response to lipopolysaccaride mediates induction of hepatic inflammatory cytokine TNFalpha. Exp Cell Res 313:1866–1876

    Article  CAS  PubMed  Google Scholar 

  26. Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V (2007) Cutting edge: Essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J Immunol 178:7516–7519

    CAS  PubMed  Google Scholar 

  27. Lukashev D, Klebanov B, Kojima H, et al (2006) Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes. J Immunol 177:4962–4965

    CAS  PubMed  Google Scholar 

  28. Thiel M, Caldwell CC, Kreth S, et al (2007) Targeted deletion of HIF-1alpha gene in T cells prevents their inhibition in hypoxic inflammed tissues and improves septic mice survival. PLoS ONE 2:e853

    Article  PubMed  Google Scholar 

  29. Bateman RM, Tokunaga C, Kareco T, Dorscheid DR, Walley KR (2007) Myocardial hypoxiainducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol 293:H448–456

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Intensive Care Medicine, University Hospital, Inselspital, 3010, Bern, Switzerland

    T. Regueira, S. M. Jakob & S. Djafarzadeh

Authors
  1. T. Regueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. M. Jakob
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Djafarzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Regueira, T., Jakob, S.M., Djafarzadeh, S. (2008). Regulation of Mitochondrial Function by Hypoxia and Inflammation in Sepsis: A Putative Role for Hypoxia Inducible Factor. In: Yearbook of Intensive Care and Emergency Medicine. Yearbook of Intensive Care and Emergency Medicine, vol 2008. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-77290-3_36

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-77290-3_36

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-77289-7

  • Online ISBN: 978-3-540-77290-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation