Foam cell induction activates ampk but uncouples its regulation of autophagy and lysosomal homeostasis
Journal article
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 and Fullerton, Morgan D.. (2020). Foam cell induction activates ampk but uncouples its regulation of autophagy and lysosomal homeostasis. International Journal of Molecular Sciences. 21(23), pp. 1-21. https://doi.org/10.3390/ijms21239033
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 and Fullerton, Morgan D. |
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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 |
Year | 2020 |
Journal | International Journal of Molecular Sciences |
Journal citation | 21 (23), pp. 1-21 |
Publisher | Multidisciplinary Digital Publishing Institute (MDPI AG) |
ISSN | 1422-0067 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/ijms21239033 |
Scopus EID | 2-s2.0-85096712263 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-21 |
Funder | National Health and Medical Research Council (NHMRC) |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 27 Nov 2020 |
Publication process dates | |
Accepted | 26 Nov 2020 |
Deposited | 02 Jun 2021 |
Grant ID | NHMRC/1085460 |
NHMRC/1078752 |
https://acuresearchbank.acu.edu.au/item/8w228/foam-cell-induction-activates-ampk-but-uncouples-its-regulation-of-autophagy-and-lysosomal-homeostasis
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Publisher's version
OA_Leblond_2020_Foam_cell_induction_activates_ampk_but.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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