HO-1 underlies resistance of AML cells to TNF-induced apoptosis

Blood
Stuart A Rushworth, David J MacEwan

Abstract

In human monocytes, tumor necrosis factor (TNF) induces a proinflammatory response. In NF-kappaB-inhibited monocytes, TNF stimulates cell death/apoptosis. In the present study, we analyzed the response of acute myeloid leukemia (AML) cells to TNF stimulation in conjunction with NF-kappaB inhibition. In all AML-derived cells tested, NF-kappaB-inhibited cells were resistant to TNF-induced apoptosis. Further investigation revealed that the cytoprotective gene heme oxygenase-1 (HO-1) was induced in NF-kappaB-inhibited AML cells in response to TNF stimulation, and HO-1 was responsible for the resistance of AML cells to the cytotoxic actions of TNF. Moreover, after transfection with HO-1 siRNA, the resistance to TNF-induced cell death signals of AML cells was removed. The HO-1 promoter region contains antioxidant-response elements that can bind the transcription factor NF-E2-related factor 2 (Nrf2). We further demonstrated that Nrf2 was activated by TNF under NF-kappaB-inhibited conditions, to play the major role in up-regulating HO-1 expression and ultimately the fate of AML cells. These results demonstrate a novel mechanism by which TNF-induced cell death is inhibited in AML cells through the induction of HO-1, via Nrf2 activation.

References

Nov 1, 1996·Science·D J Van AntwerpI M Verma
Nov 7, 1998·The Journal of Biological Chemistry·M A O'ConnellN Mackman
Oct 4, 2000·The Journal of Experimental Medicine·S BrouardM P Soares
Oct 11, 2001·American Journal of Physiology. Renal Physiology·N Hill-KapturczakA Agarwal
Mar 5, 2002·Nature Medicine·Tzong-Shyuan Lee, Lee-Young Chau
Mar 19, 2002·Cellular Signalling·David J MacEwan
Nov 19, 2002·The Journal of Biological Chemistry·E Christine PietschSuzy V Torti
Aug 12, 2003·Trends in Immunology·Leo E OtterbeinFritz H Bach
Oct 1, 2003·Angiogenesis·Makoto SunamuraNader G Abraham
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongtao LiuRichard M Pope
Apr 28, 2004·Free Radical Biology & Medicine·Anil K Jaiswal
May 1, 2004·Science·Dennis Normile
Aug 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Steven J TuckerDavid J MacEwan
Oct 28, 2004·Biochemical Society Transactions·S A Rushworth, M A O'Connell
Dec 2, 2004·Molecular and Cellular Biology·Donna D ZhangMark Hannink
Jun 17, 2005·The New England Journal of Medicine·Paul G RichardsonUNKNOWN Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators
Jul 7, 2005·The Journal of Experimental Medicine·Tirumalai RangasamyShyam Biswal
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stuart A RushworthMaria A O'Connell
Dec 2, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marcelo HillIgnacio Anegon
Feb 8, 2006·Biochemical and Biophysical Research Communications·Stuart A RushworthMaria A O'Connell
Apr 6, 2006·The Journal of Clinical Investigation·Rajesh K ThimmulappaShyam Biswal
Mar 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eleuterio LombardoUlla G Knaus
Jul 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Colin RaeDavid J MacEwan
Feb 8, 2008·Cell Cycle·Stuart A RushworthDavid J MacEwan

❮ Previous
Next ❯

Citations

Mar 3, 2011·Archives of Toxicology·Liam Baird, Albena T Dinkova-Kostova
Mar 12, 2010·Cell Biology and Toxicology·Ghada AbdelhamidAyman O S El-Kadi
Aug 21, 2012·Antioxidants & Redox Signaling·Mary E IrwinJoya Chandra
Aug 15, 2009·Human Molecular Genetics·Cécile VercheratReshma Taneja
Sep 24, 2013·Antioxidants & Redox Signaling·Magdalena KozakowskaAlicja Jozkowicz
Dec 26, 2013·Cancer Immunology, Immunotherapy : CII·Jürgen C BeckerMads Hald Andersen
Jul 9, 2010·Molekuliarnaia biologiia·E B Men'shikovaN K Zenkov
Jan 27, 2015·International Journal of Molecular Sciences·Christine RichardsonC Greer Vestal
Sep 20, 2012·Biochemical and Biophysical Research Communications·Jean-Yves TanoGuillermo Vazquez
Dec 7, 2011·Free Radical Biology & Medicine·Anna Lisa FurfaroNicola Traverso
Oct 8, 2011·Cellular Signalling·Megan Y MurrayDavid J MacEwan
Mar 19, 2011·Biochemical and Biophysical Research Communications·Jean-Yves Tano, Guillermo Vazquez
Jul 27, 2010·Trends in Cardiovascular Medicine·Katarína LarsenHenricus J Duckers
Mar 10, 2009·Progress in Neuro-psychopharmacology & Biological Psychiatry·Monika A PapiezGabriel Nowak
Mar 3, 2009·Advanced Drug Delivery Reviews·Jun FangHiroshi Maeda
Dec 31, 2010·British Journal of Pharmacology·Stuart A Rushworth
Apr 5, 2016·Nature Communications·Reshmi ParameswaranDavid N Wald
Aug 12, 2014·Biochemical Society Transactions·David J MacEwanLyubov Zaitseva
Nov 10, 2013·Free Radical Biology & Medicine·Hye-Kyung Na, Young-Joon Surh
May 13, 2015·Molecular Therapy. Nucleic Acids·Breanne LandryHasan Uludag
May 24, 2012·Cell Cycle·Lawrence N BarreraDavid J MacEwan
Sep 13, 2008·Journal of the American College of Cardiology·Naglaa K IdrissGregory Y H Lip
Jul 4, 2013·Free Radical Biology & Medicine·Irene Gañán-GómezGuillermo García-Manero
Sep 23, 2008·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Armin GerbitzErnst Holler
Apr 29, 2015·Oxidative Medicine and Cellular Longevity·Amina Abdul-AzizStuart A Rushworth

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

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

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.