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- Title
Loss of Sirtuin 1 (SIRT1) potentiates endothelial dysfunction via impaired glycolysis during infectious challenge.
- Authors
Stark, Ryan J.; Koch, Stephen R.; Stothers, Cody L.; Pourquoi, Allison; Lamb, Celia K.; Miller, Michael R.; Choi, Hyehun
- Abstract
Sepsis is an exaggerated host response to infection that despite advances in early recognition and intervention, remains a common cause of morbidity and mortality.1,2 The pathophysiology is related to global inflammation and cytokinemia driving endothelial dysfunction to produce the prototypic signs of vasculopathy such as altered vasomotor tone and capillary leak.3-5 Silent information regulator 2 (Sir2) proteins (sirtuins), are a class of seven NAD-dependent deacetylases or ADP-ribosyltransferases that regulate cellular homeostasis.6 Sirtuin 1 (SIRT1) is the best characterised, specifically related to cellular metabolism.7 The effects of SIRT1 have been postulated to be mediated by endothelial nitric oxide synthase (eNOS), forkhead box O1(FOXO1), peroxisome proliferator-activated receptor- coactivator 1 (PGC1 ) and mitochondrial transcription factor A (TFAM). Associated representative confocal images (40×, line bar represents a distance of 50 m) are shown for SIRT1-eNOS (cyan), SIRT1-FOXO1 (purple) and SIRT1-TFAM (red) PLA reactions. n = 5 individual replicates per group. To explore if expression was protective, we applied EX527, a SIRT1 inhibitor or siRNA to SIRT1 (siSIRT1) prior to LPS.
- Subjects
SIRTUINS; GLYCOLYSIS; ENDOTHELIUM diseases; FORKHEAD transcription factors; TRANSCRIPTION factors
- Publication
Clinical & Translational Medicine, 2022, Vol 12, Issue 9, p1
- ISSN
2001-1326
- Publication type
Article
- DOI
10.1002/ctm2.1054