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J Crit Care. 2018 Feb;43:197-201. doi: 10.1016/j.jcrc.2017.09.012. Epub 2017 Sep 8.

Overcoming the Warburg Effect: Is it the key to survival in sepsis?

Author information

1
Trauma Research Dept, Swedish Medical Center, Englewood, CO 80113, USA; Trauma Research Dept, Medical Center of Plano, Plano, TX 75075, USA; Trauma Research Dept, St. Anthony Hospital, Lakewood, CO 80228, USA; Trauma Research Dept, Penrose Hospital, Colorado Springs, CO 80907, USA. Electronic address: dbaror@ampiopharma.com.
2
Trauma Research Dept, Medical Center of Plano, Plano, TX 75075, USA.
3
Trauma Research Dept, Penrose Hospital, Colorado Springs, CO 80907, USA.
4
Trauma Research Dept, Research Medical Center, Kansas City, MO 64132, USA.
5
Trauma Research Dept, Swedish Medical Center, Englewood, CO 80113, USA.
6
Somalogic Inc., Boulder, CO 80301, USA.

Abstract

Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions). Although the initial pathways of cancer and sepsis may be different, the mechanisms which allow aerobic glycolysis to occur, even in the presence of oxygen, are similar. This review provides some evidence that reversing these steps reverses the Warburg Effect in model systems and some pathological consequences of this effect. Therefore, this implies that these steps might be modifiable in sepsis to reverse the Warburg Effect and possibly lead to better outcomes.

KEYWORDS:

Glycolysis; Metabolism; Oxidative phosphorylation; Sepsis; Warburg effect

PMID:
28915394
DOI:
10.1016/j.jcrc.2017.09.012
[Indexed for MEDLINE]

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