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- Title
Foam Cell Induction Activates AMPK But Uncouples Its Regulation of Autophagy and Lysosomal Homeostasis.
- Authors
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.
- Subjects
LYSOSOMES; AUTOPHAGY; HOMEOSTASIS; FOAM cells; MACROPHAGES; PROTEIN kinases
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 23, p9033
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21239033