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REVIEW ARTICLE
Year : 2018  |  Volume : 5  |  Issue : 1  |  Page : 3-21

Fundamental role of warburg effect in various pathophysiological processes


Department of Physiology, Christian Medical College, Vellore, Tamil Nadu, India

Correspondence Address:
Dr. Vasanthakumar Natesan
Department of Physiology, Christian Medical College, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijcep.ijcep_55_17

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In this review article, the role of Warburg effect in various pathologies is discussed using septic shock as the base model. I had proposed a slightly extended Warburg effect which I would like to call it as “Warburg common pathogenesis model or Warburg differentiation–dedifferentiation effect,” which has the potential to explain septic shock and sepsis-associated multiorgan dysfunction and many other major pathologies such as systemic hypertension, pulmonary arterial hypertension, congestive heart failure, diabetes mellitus, asthma, acute respiratory distress syndrome, and acute kidney injury, implying that most of the diseases may have a common pathogenesis as the underlying mechanism. Increased nitric oxide (NO) in sepsis via inducible nitric oxide synthase (iNOS) or any respiratory poison, in general, irreversibly inhibits the mitochondrial respiration and shifts the metabolic phenotype of the cell from oxidative phosphorylation to glycolytic phenotype, and the change in metabolic phenotype is followed by the change in cell phenotype from the normal adult dynamic differentiation state to irreversible dedifferentiation states – embryonic phenotype, synthetic/proliferative phenotype, and cancer phenotype. This dedifferentiated state switching can be seen as the cells' local survival strategy in response to injuries, but returning to their primitive forms leads to disorder and ends in global collapse of the organ systems and organism which requires order in terms of differentiation. Treatment in most of the pathologies should aim at reversing Warburg effect by the activation of mitochondrial respiration, thereby decreasing the aerobic glycolysis and changing the cell to its normal adult dynamic differentiation phenotype, i.e. all the drugs are used here as differentiation therapy. Adrenergic blockers and ascorbic acid may be the main treatment options, which are already used by some research groups. Even though high NO via iNOS was involved in most of the pathologies including sepsis, any substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect and irreversible dedifferentiation. A mild and reversible Warburg differentiation–dedifferentiation effect may be necessary for normal functioning, and the same effect in exaggerated and irreversible way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the diseases including septic shock.


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