Journal article
Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism, and vasodilation
Journal of cell science, Vol.137(24), jcs262232
12/15/2024
DOI: 10.1242/jcs.262232
PMCID: PMC11795286
PMID: 39513477
Appears in UI Libraries Support Open Access
Abstract
Endothelial cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that the application of force to endothelial cells stimulates VE-cadherin to activate liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin stimulated AMPK increases eNOS activity and localization to the plasma membrane, reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake. We present evidence for the increase in metabolism being necessary to fortify the adhesion complex, actin cytoskeleton, and cellular alignment. Together these data extend the paradigm for how mechanotransduction and metabolism are linked to include a connection to vasodilation, thereby providing new insight into how diseases involving contractile, metabolic, and vasodilatory disturbances arise.
Details
- Title: Subtitle
- Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism, and vasodilation
- Creators
- Nicholas M. Cronin - University of IowaLogan W. Dawson - University of IowaKris A. DeMali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.137(24), jcs262232
- DOI
- 10.1242/jcs.262232
- PMID
- 39513477
- PMCID
- PMC11795286
- NLM abbreviation
- J Cell Sci
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Publisher
- The Company of Biologists; CAMBRIDGE
- Grant note
- National Institutes of Health: R35GM136291, P30CA086862 Predoctoral Training in the Pharmacological Sciences: T32GM144636-01 University of Iowa
This work is supported by National Institutes of Health (grants #R35GM136291 to K.A.D. and P30CA086862 to the Holden Comprehensive Cancer Center) . L.W.D. is supported by the Predoctoral Training in the Pharmacological Sciences #T32GM144636-01. Open Access funding provided by University of Iowa. Deposited in PMC for immediate release.
- Language
- English
- Electronic publication date
- 11/08/2024
- Date published
- 12/15/2024
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984747078002771
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