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Foam cell induction activates ampk but uncouples its regulation of autophagy and lysosomal homeostasis
LeBlond, Nicholas D. Nunes, Julia R. C. Smith, Tyler K. T. O’Dwyer, Conor Robichaud, Sabrina Gadde, Suresh Côté, Marceline Kemp, Bruce E. Ouimet, Mireille Fullerton, Morgan D.
LeBlond, Nicholas D.
Nunes, Julia R. C.
Smith, Tyler K. T.
O’Dwyer, Conor
Robichaud, Sabrina
Gadde, Suresh
Côté, Marceline
Kemp, Bruce E.
Ouimet, Mireille
Fullerton, Morgan D.
Abstract
The dysregulation of macrophage lipid metabolism drives atherosclerosis. AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics and plays essential roles regulating macrophage lipid dynamics. Here, we investigated the consequences of atherogenic lipoprotein-induced foam cell formation on downstream immunometabolic signaling in primary mouse macrophages. A variety of atherogenic low-density lipoproteins (acetylated, oxidized, and aggregated forms) activated AMPK signaling in a manner that was in part due to CD36 and calcium-related signaling. In quiescent macrophages, basal AMPK signaling was crucial for maintaining markers of lysosomal homeostasis as well as levels of key components in the lysosomal expression and regulation network. Moreover, AMPK activation resulted in targeted upregulation of members of this network via transcription factor EB. However, in lipid-induced macrophage foam cells, neither basal AMPK signaling nor its activation affected lysosomal-associated programs. These results suggest that while the sum of AMPK signaling in cultured macrophages may be anti-atherogenic, atherosclerotic input dampens the regulatory capacity of AMPK signaling.
Keywords
macrophage, AMP-activated protein kinase (AMPK), autophagy, immunometabolism, lysosomal homeostasis, atherosclerosis, foam cell, lipids
Date
2020
Type
Journal article
Journal
International Journal of Molecular Sciences
Book
Volume
21
Issue
23
Page Range
1-21
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open