NDLI: Platelets Promote Mitochondrial Uncoupling and Resistance to Apoptosis in Leukemia Cells: A Novel Paradigm for the Bone Marrow Microenvironment

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Platelets Promote Mitochondrial Uncoupling and Resistance to Apoptosis in Leukemia Cells: A Novel Paradigm for the Bone Marrow Microenvironment

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Platelets Promote Mitochondrial Uncoupling and Resistance to Apoptosis in Leukemia Cells: A Novel Paradigm for the Bone Marrow Microenvironment

Content Provider	Springer Nature Link
Author	Velez, Juliana Enciso, Leonardo José Suarez, Marta Fiegl, Michael Grismaldo, Adriana López, Catalina Barreto, Alfonso Cardozo, Claudia Palacios, Pilar Morales, Ludis Duque, Jorge Eduardo Carmona, Jorge Uriel Konopleva, Marina Andreeff, Michael Samudio, Ismael
Copyright Year	2014
Abstract	Here we report that leukemia cell lines and primary CD34+ leukemic blasts exposed to platelet rich plasma (PRP) or platelet lysates (PL) display increased resistance to apoptosis induced by mitochondria-targeted agents ABT-737 and CDDO-Me. Intriguingly, leukemia cells exposed to platelet components demonstrate a reduction in mitochondrial membrane potential (ΔΨM) and a transient increase in oxygen consumption, suggestive of mitochondrial uncoupling. Accompanying the ranolazine-sensitive increase in oxygen consumption, a reduction in triglyceride content was also observed in leukemia cells cultured with platelet components indicating that lipolysis and fatty acid oxidation may support the molecular reduction of oxygen in these cells. Mechanistically, platelet components antagonized Bax oligomerization in accordance with previous observations supporting an antiapoptotic role for fatty acid oxidation in leukemia cells. Lastly, substantiating the notion that mitochondrial uncoupling reduces oxidative stress, platelet components induced a marked decrease in basal and rotenone-induced superoxide levels in leukemia cells. Taken together, the decrease in ΔΨM, the transient increase in ranolazine-sensitive oxygen consumption, the reduction in triglyceride levels, and the reduced generation of superoxide, all accompanying the increased resistance to mitochondrial apoptosis, substantiate the hypothesis that platelets may contribute to the chemoprotective sanctuary of the bone marrow microenvironment via promotion of mitochondrial uncoupling.
Starting Page	79
Ending Page	90
Page Count	12
File Format	PDF
ISSN	18752292
Journal	Cancer Microenvironment
Volume Number	7
Issue Number	1-2
e-ISSN	18752284
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-08-12
Publisher Institution	International Cancer Microenvironment Society
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Platelets Leukemia Apoptosis Fatty acid oxidation Metabolism Mitochondrial uncoupling CDDO-Me ABT-737 Cancer Research Oncology Immunology Cell Biology Biochemistry Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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