PPARa and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia

نویسندگان

  • Stephanie Tung
  • Yonghong Shi
  • Karry Wong
  • Fang Zhu
  • Reg Gorczynski
  • Robert C. Laister
  • Mark Minden
  • Anne-Kareen Blechert
  • Yvonne Genzel
  • Udo Reichl
  • David E. Spaner
چکیده

Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Medical Biophysics, and Department of Immunology, University of Toronto, Toronto, ON, Canada; Transplant Research Division, Toronto General Hospital, Toronto, ON, Canada; Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering Group, Magdeburg, Germany; and Sunnybrook Odette Cancer Center, Toronto, ON, Canada

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منابع مشابه

PPARα and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia.

High-dose glucocorticoids (GCs) can be a useful treatment for aggressive forms of chronic lymphocytic leukemia (CLL). However, their mechanism of action is not well understood, and resistance to GCs is inevitable. In a minimal, serum-free culture system, the synthetic GC dexamethasone (DEX) was found to decrease the metabolic activity of CLL cells, indicated by down-regulation of pyruvate kinas...

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Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha

BACKGROUND Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. METHODS Mice were pre...

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Investigating and targeting chronic lymphocytic leukemia metabolism with the human immunodeficiency virus protease inhibitor ritonavir and metformin.

Chronic lymphocytic leukemia (CLL) remains fatal due to the development of resistance to existing therapies. Targeting abnormal glucose metabolism sensitizes various cancer cells to chemotherapy and/or elicits toxicity. Examination of glucose dependency in CLL demonstrated variable sensitivity to glucose deprivation. Further evaluation of metabolic dependencies of CLL cells resistant to glucose...

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Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function.

RATIONALE Fatty acid oxidation is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)α and under normal conditions accounts for 70% of cardiac ATP content. Reduced Ppara expression during sepsis and heart failure leads to reduced fatty acid oxidation and myocardial energy deficiency. Many of the transcriptional regulators of Ppara are unknown. OBJECTIVE To determi...

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تاریخ انتشار 2013