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Full-Text Articles in Medicine and Health Sciences

Lipid-Induced Epigenomic Changes In Human Macrophages Identify A Coronary Artery Disease-Associated Variant That Regulates Ppap2b Expression Through Altered C/Ebp-Beta Binding, Michael E. Reschen, Kyle J. Gaulton, Da Lin, Elizabeth J. Soilleux, Andrew J. Morris, Susan S. Smyth, Christopher A. O'Callaghan Apr 2015

Lipid-Induced Epigenomic Changes In Human Macrophages Identify A Coronary Artery Disease-Associated Variant That Regulates Ppap2b Expression Through Altered C/Ebp-Beta Binding, Michael E. Reschen, Kyle J. Gaulton, Da Lin, Elizabeth J. Soilleux, Andrew J. Morris, Susan S. Smyth, Christopher A. O'Callaghan

Gill Heart & Vascular Institute Faculty Publications

Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at the majority of loci are unknown. Recent studies have suggested that many causal GWAS variants influence disease through altered transcriptional regulation in disease-relevant cell types. We explored changes in transcriptional regulation during a key pathophysiological event in CAD, the environmental lipid-induced transformation of macrophages to lipid-laden foam cells. We used a combination of open chromatin mapping with formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and enhancer and transcription factor mapping using chromatin immuno-precipitation (ChIP-seq) in primary human macrophages before …


Metabolic Reprogramming Of Cancer-Associated Fibroblasts By Idh3Α Downregulation, Daoxiang Zhang, Yongbin Wang, Zhimin Shi, Jingyi Liu, Pan Sun, Xiaodan Hou, Jian Zhang, Shimin Zhao, Binhua P. Zhou, Jun Mi Mar 2015

Metabolic Reprogramming Of Cancer-Associated Fibroblasts By Idh3Α Downregulation, Daoxiang Zhang, Yongbin Wang, Zhimin Shi, Jingyi Liu, Pan Sun, Xiaodan Hou, Jian Zhang, Shimin Zhao, Binhua P. Zhou, Jun Mi

Markey Cancer Center Faculty Publications

Cancer-associated fibroblasts (CAFs) provide critical metabolites for tumor growth and undergo metabolic reprogramming to support glycolysis. However, the molecular mechanisms responsible for this change remain unclear. Here, we report that TGF-β1- or PDGF-induced CAFs switch from oxidative phosphorylation to aerobic glycolysis. We identify downregulation of isocitrate dehydrogenase 3α (IDH3α) as a marker for this switch. Furthermore, miR-424 downregulates IDH3α during CAF formation. Downregulation of IDH3α decreases the effective level of α-ketoglutarate (α-KG) by reducing the ratio of α-KG to fumarate and succinate, resulting in PHD2 inhibition and HIF-1α protein stabilization. The accumulation of HIF-1α, in turn, promotes glycolysis by increasing …


Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer Mar 2015

Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the …