2023
DOI: 10.1111/bph.16050
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Piezo1 channel activation stimulates ATP production through enhancing mitochondrial respiration and glycolysis in vascular endothelial cells

Abstract: Background and Purpose Piezo1 channels are mechanosensitive cationic channels that are activated by mechanical stretch or shear stress. Endothelial Piezo1 activation by shear stress caused by blood flow induces ATP release from endothelial cells; however, the link between shear stress and endothelial ATP production is unclear. Experimental Approach The mitochondrial respiratory function of cells was measured by using high‐resolution respirometry system Oxygraph‐2k. The intracellular Ca2+ concentration was eval… Show more

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Cited by 21 publications
(6 citation statements)
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“…GSIS is also regulated by metabolic cell signaling events within glycolysis, particularly activation of PFK, which regulates the rate-limiting step glucokinase and has been shown to be regulated by changes in intracellular Ca 2+ [53] , [77] , [78] . Our results showing increased PFK activity with increased RTG stiffness are aligned with results in other cells types and support a potential role for altered glycolysis rates in contributing to increases in insulin secretion at low glucose as increased rates of glycolysis mediate membrane depolarization and insulin exocytosis [79] . Additionally, inhibiting Piezo1 in mouse islets encapsulated in stiff RTG decreased PFK activity.…”
Section: Discussionsupporting
confidence: 87%
See 1 more Smart Citation
“…GSIS is also regulated by metabolic cell signaling events within glycolysis, particularly activation of PFK, which regulates the rate-limiting step glucokinase and has been shown to be regulated by changes in intracellular Ca 2+ [53] , [77] , [78] . Our results showing increased PFK activity with increased RTG stiffness are aligned with results in other cells types and support a potential role for altered glycolysis rates in contributing to increases in insulin secretion at low glucose as increased rates of glycolysis mediate membrane depolarization and insulin exocytosis [79] . Additionally, inhibiting Piezo1 in mouse islets encapsulated in stiff RTG decreased PFK activity.…”
Section: Discussionsupporting
confidence: 87%
“…These results suggest that mechanotransduction by the Piezo1 channel may also regulate islet metabolism that could contribute to altered insulin secretion. Previous studies in other cell types show Piezo1 closure boosts ATP production and promotes glycolysis and that altered intracellular Ca 2+ may regulate the activity of PFK [53] , [79] . While outside of the scope of the current work, future studies will determine if Piezo1 regulates the islet response to mechanical cues through Ca 2+ -mediated upregulation PFK activity and dysfunctional GSIS.…”
Section: Discussionmentioning
confidence: 89%
“…The activated Piezo1 promotes the shift of macrophages metabolism into aerobic glycolysis and increases the secretion of IL-1β, IL-6, TNF-α, while knock-out of Piezo1 inhibits aerobic glycolysis in colon macrophages of colitis induced by dextran sulfate sodium salt [ 65 ]. Similarly, Piezo1 reportedly enhances anaerobic glycolysis and mitochondrial respiration in vascular endothelial cell to stimulate ATP production [ 134 ], further indicating a significant association between mechanosensitive Piezo1 and glucose metabolism.…”
Section: Piezo1 Affects the Biological Function Of The Digestive Systemmentioning
confidence: 99%
“…Stretch-activated ion channels (SACs), integrins, cadherins, G protein-coupled receptors, caveolae, cytoskeletal filaments, nuclei, the ECM, force-sensitive kinases and numerous other structures and signaling molecules have all been shown to contribute to the mechanosensitive and mechanotransductive responses. 3 Of note, mechanotransduction is not limited to classical signaling pathways but also includes metabolic changes 4 (such as glycolysis, 5,6 cholesterol synthesis, [7][8][9] iron metabolism, 10 and water metabolism 11,12 ), chromatin organization, and gene expression. 13 Among the various mechanosensors, mechanosensitive ion channels (MSCs) are unique due to their distinctive properties.…”
Section: Introductionmentioning
confidence: 99%