Pregledni rad

Metabolism and differentiation

DORA VIŠNJIĆ ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia
HRVOJE LALIĆ ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia
VILMA DEMBITZ ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia
HRVOJE BANFIĆ ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia

Sažetak

Textbook biochemical pathways do not usually apply to intermediary
metabolism of highly proliferating, differentiating, or tumor cells. Over 80 years ago, Otto Warburg observed that cancer cells, unlike normal cells, favor glycolysis for energy production, even under aerobic conditions, and proposed that this shift in cancer cell metabolism (termed „aerobic glycolysis”) was due to mitochondrial dysfunction. Recent studies by several groups suggest that aerobic glycolysis in tumor cells is actually caused by oncogene-directed changes in metabolism that are necessary for both continuous proliferation
and a block in cellular differentiation.


Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin
(mTOR) is one of the principal proliferative and anti-apoptotic signaling
pathways, which is known to support glycolysis and anabolism. Our previous studies demonstrated the activation of PI3K and Akt in nuclei of leukemia cells during differentiation, and confirmed that the inhibition of proximal components of the pathway inhibits proliferation, but negatively affects differentiative capacity of the cells. In contrast, use of rapamycin, which inhibits mTOR, a more distal component of the pathway, potentiates differentiation along granulocytic pathway. To further investigate the role of upstream regulators of mTOR in leukemia differentiation, we tested the effects of modulators of AMP-activated protein kinase (AMPK). Our results suggest a strong differentiative property of an AMPK activator, AICAR (5-amino-1-b-D-ribofuranosyl-imidazole-4-carboxamide) in monocytic U937 cells. The mechanism of AICAR-mediated effects will be presented and a possible role of AMPK-modulators in differentiation therapy will be discussed.

Ključne riječi

Metabolism; Differentiation; Leukemia

Hrčak ID:

125482

URI

https://hrcak.srce.hr/125482

Datum izdavanja:

31.3.2014.

Posjeta: 1.584 *