Mitochondrial dysfunction during sepsis, impact and possible regulating role of hypoxia-inducible factor-1alpha

Medicina intensiva
T RegueiraS Djafarzadeh

Abstract

There is a direct correlation between the development of the multiple organ dysfunction syndrome (MODS) and the elevated mortality associated with sepsis. The mechanisms responsible for MODS development are being studied, however, the main efforts regarding MODS evaluation have focused on oxygen delivery optimization and on the modulation of the characteristic inflammatory cascade of sepsis, all with negative results. Recent studies have shown that there is development of tissue acidosis, even when there are normal oxygen conditions and limited presence of tissue cellular necrosis or apoptosis, which would indicate that cellular energetic dysfunction may be a central element in MODS pathogenesis. Mitochondrias are the main source of cellular energy, central regulators of cell death and the main source for reactive oxygen species. Several mechanisms contribute to mitochondrial dysfunction during sepsis, that is blockage of pyruvate entry into the Krebs cycle, oxidative phosphorylation substrate use in other enzymatic complexes, enzymatic complex inhibition and membrane damage mediated by oxidative stress, and reduction in mitochondrial content. Hypoxia-inducible factor-1alpha (HIF-1alpha) is a nuclear transcription factor with a...Continue Reading

References

Jun 16, 1994·The New England Journal of Medicine·M A HayesD Watson
Oct 6, 1997·Archives of Biochemistry and Biophysics·S P KantrowC A Piantadosi
Aug 14, 1999·Critical Care Medicine·R S HotchkissI E Karl
Feb 2, 2002·Science·David LandoMurray L Whitelaw
Mar 13, 2002·Critical Care Medicine·Elliott D CrouserDouglas R Pfeiffer
May 30, 2002·Biological Chemistry·Rafael RadiRoberto Hodara
Mar 12, 2003·Cell·Thorsten CramerRandall S Johnson
Apr 12, 2003·Critical Care Medicine·Edward Abraham
Nov 8, 2003·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David BrealeyMervyn Singer
Dec 13, 2005·Critical Care Medicine·Paul T Schumacker
Jan 21, 2006·Critical Care Medicine·Jean-Louis VincentUNKNOWN Sepsis Occurrence in Acutely Ill Patients Investigators
Feb 14, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Andrey V KozlovHeinz Redl

❮ Previous
Next ❯

Citations

May 10, 2011·Medicina intensiva·T RegueiraP Downey
Feb 2, 2017·International Journal of Hematology·Jesus Reyna-FigueroaVicente Madrid-Marina

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.