Single-molecule quantification of lipotoxic expression of activating transcription factor 3

Yahiatene I, Aung HH, Wilson DW, Rutledge JC (2014)
Physical Chemistry Chemical Physics 16(39): 21595-21601.

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Activating transcription factor 3 (ATF3) is a member of the mammalian activation transcription factor/cAMP, physiologically important in the regulation of pro- and anti-inflammatory target genes. We compared the induction of ATF3 protein as measured by Western blot analysis with single-molecule localization microscopy dSTORM to quantify the dynamics of accumulation of intranuclear ATF3 of triglyceride-rich (TGRL) lipolysis product-treated HAEC (Human Aortic Endothelial Cells). The ATF3 expression rate within the first three hours after treatment with TGRL lipolysis products is about 3500 h(-1). After three hours we detected 33 090 3491 single-molecule localizations of ATF3. This was accompanied by significant structural changes in the F-actin network of the cells at similar to 3-fold increased localization precision compared to widefield microscopy after treatment. Additionally, we discovered a cluster size of approximately 384 nanometers of ATF3 molecules. We show for the first time the time course of ATF3 accumulation in the nucleus undergoing lipotoxic injury. Furthermore, we demonstrate ATF3 accumulation associated with increased concentrations of TGRL lipotysis products occurs in large aggregates.
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Yahiatene I, Aung HH, Wilson DW, Rutledge JC. Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Physical Chemistry Chemical Physics. 2014;16(39):21595-21601.
Yahiatene, I., Aung, H. H., Wilson, D. W., & Rutledge, J. C. (2014). Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Physical Chemistry Chemical Physics, 16(39), 21595-21601. doi:10.1039/c4cp03260h
Yahiatene, I., Aung, H. H., Wilson, D. W., and Rutledge, J. C. (2014). Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Physical Chemistry Chemical Physics 16, 21595-21601.
Yahiatene, I., et al., 2014. Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Physical Chemistry Chemical Physics, 16(39), p 21595-21601.
I. Yahiatene, et al., “Single-molecule quantification of lipotoxic expression of activating transcription factor 3”, Physical Chemistry Chemical Physics, vol. 16, 2014, pp. 21595-21601.
Yahiatene, I., Aung, H.H., Wilson, D.W., Rutledge, J.C.: Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Physical Chemistry Chemical Physics. 16, 21595-21601 (2014).
Yahiatene, Idir, Aung, Hnin H., Wilson, Dennis W., and Rutledge, John C. “Single-molecule quantification of lipotoxic expression of activating transcription factor 3”. Physical Chemistry Chemical Physics 16.39 (2014): 21595-21601.
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3 Citations in Europe PMC

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Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet.
Rutkowsky JM, Lee LL, Puchowicz M, Golub MS, Befroy DE, Wilson DW, Anderson S, Cline G, Bini J, Borkowski K, Knotts TA, Rutledge JC, Mouse Metabolic Phenotyping Center Imaging Working Group., PLoS One 13(2), 2018
PMID: 29444171
Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress.
Lee LL, Aung HH, Wilson DW, Anderson SE, Rutledge JC, Rutkowsky JM., Am J Physiol Cell Physiol 312(4), 2017
PMID: 28077357
Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways.
Aung HH, Altman R, Nyunt T, Kim J, Nuthikattu S, Budamagunta M, Voss JC, Wilson D, Rutledge JC, Villablanca AC., J Lipid Res 57(6), 2016
PMID: 27087439

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