Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins

OBJECTIVE-: Oxidized low-density lipoprotein (oxLDL) induces survival of colony stimulating factor-1 (CSF-1)-dependent macrophages in vitro. Because atherosclerotic lesion-associated macrophages take up large amounts of glucose, we investigated whether, and how, oxLDL promotes glucose uptake and how...

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Main Authors: Elsegood, Caryn, Chang, M., Jessup, W., Scholz, G., Hamilton, J.
Format: Journal Article
Published: Lippincott Williams & Wilkins 2009
Online Access:http://hdl.handle.net/20.500.11937/21809
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author Elsegood, Caryn
Chang, M.
Jessup, W.
Scholz, G.
Hamilton, J.
author_facet Elsegood, Caryn
Chang, M.
Jessup, W.
Scholz, G.
Hamilton, J.
author_sort Elsegood, Caryn
building Curtin Institutional Repository
collection Online Access
description OBJECTIVE-: Oxidized low-density lipoprotein (oxLDL) induces survival of colony stimulating factor-1 (CSF-1)-dependent macrophages in vitro. Because atherosclerotic lesion-associated macrophages take up large amounts of glucose, we investigated whether, and how, oxLDL promotes glucose uptake and how glucose metabolism regulates oxLDL-induced macrophage survival. METHODS AND RESULTS-: OxLDL-induced macrophage survival required glucose metabolism. OxLDL stimulated 2 phases of glucose uptake, namely acute and chronic, which required PI3K but not MEK1/2 activity. PI3K appeared to regulate glucose transport via glucose transporter affinity and/or mobilization. OxLDL also maintained levels of the prosurvival proteins, Bcl-2 and Bcl-xL, after CSF-1 had been removed through a combination of mechanisms including transcription, translation, and protein stabilization. Significantly, inhibition of glucose metabolism reduced Bcl-2 and Bcl-xL protein levels. MEK1/2 and PI3K activities were also required for oxLDL-induced Bcl-2 and Bcl-xL mRNA upregulation. CONCLUSIONS-: These results suggest that oxLDL enhances macrophage survival in the absence of CSF-1 by inducing PI3K-dependent glucose uptake, which is metabolized to maintain Bcl-2 and Bcl-xL protein levels. © 2009 American Heart Association, Inc.
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spelling curtin-20.500.11937-218092017-09-13T13:54:25Z Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins Elsegood, Caryn Chang, M. Jessup, W. Scholz, G. Hamilton, J. OBJECTIVE-: Oxidized low-density lipoprotein (oxLDL) induces survival of colony stimulating factor-1 (CSF-1)-dependent macrophages in vitro. Because atherosclerotic lesion-associated macrophages take up large amounts of glucose, we investigated whether, and how, oxLDL promotes glucose uptake and how glucose metabolism regulates oxLDL-induced macrophage survival. METHODS AND RESULTS-: OxLDL-induced macrophage survival required glucose metabolism. OxLDL stimulated 2 phases of glucose uptake, namely acute and chronic, which required PI3K but not MEK1/2 activity. PI3K appeared to regulate glucose transport via glucose transporter affinity and/or mobilization. OxLDL also maintained levels of the prosurvival proteins, Bcl-2 and Bcl-xL, after CSF-1 had been removed through a combination of mechanisms including transcription, translation, and protein stabilization. Significantly, inhibition of glucose metabolism reduced Bcl-2 and Bcl-xL protein levels. MEK1/2 and PI3K activities were also required for oxLDL-induced Bcl-2 and Bcl-xL mRNA upregulation. CONCLUSIONS-: These results suggest that oxLDL enhances macrophage survival in the absence of CSF-1 by inducing PI3K-dependent glucose uptake, which is metabolized to maintain Bcl-2 and Bcl-xL protein levels. © 2009 American Heart Association, Inc. 2009 Journal Article http://hdl.handle.net/20.500.11937/21809 10.1161/ATVBAHA.108.180778 Lippincott Williams & Wilkins unknown
spellingShingle Elsegood, Caryn
Chang, M.
Jessup, W.
Scholz, G.
Hamilton, J.
Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins
title Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins
title_full Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins
title_fullStr Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins
title_full_unstemmed Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins
title_short Glucose metabolism is required for oxidized LDL-induced macrophage survival: Role of PI3K and Bcl-2 family proteins
title_sort glucose metabolism is required for oxidized ldl-induced macrophage survival: role of pi3k and bcl-2 family proteins
url http://hdl.handle.net/20.500.11937/21809