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#35708204 2022/06/16 To Up
Molecular characteristics of the multi-functional FAO enzyme ACAD9 illustrate the importance of FADH /NADH ratios for mitochondrial ROS formation.A decade ago I postulated that ROS formation in mitochondria was influenced by different FADH /NADH (F/N) ratios of catabolic substrates. Thus, fatty acid oxidation (FAO) would give higher ROS formation than glucose oxidation. Both the emergence of peroxisomes and neurons not using FAO, could be explained thus. ROS formation in NADH:ubiquinone oxidoreductase (Complex I) comes about by reverse electron transport (RET) due to high QH levels, and scarcity of its electron-acceptor (Q) during FAO. The then new, unexpected, finding of an FAO enzyme, ACAD9, being involved in complex I biogenesis, hinted at connections in line with the hypothesis. Recent findings about ACAD9's role in regulation of respiration fit with predictions the model makes: cementing connections between ROS production and F/N ratios. I describe how ACAD9 might be central to reversing the oxidative damage in complex I resulting from FAO. This seems to involve two distinct, but intimately connected, ACAD9 characteristics: (i) its upregulation of complex I biogenesis, and (ii) releasing FADH , with possible conversion into FMN, the crucial prosthetic group of complex I. Also see the video abstract here: https://youtu.be/N7AT_HBNumg.
2016 related Products with: Molecular characteristics of the multi-functional FAO enzyme ACAD9 illustrate the importance of FADH /NADH ratios for mitochondrial ROS formation.500 Units100 U1100.00 ul 100 G1200 units100 500IU
#35461379 2022/04/23 To Up
Whole-genome sequencing analysis of clozapine-induced myocarditis.One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (pâ<â0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Ankita Narang, Paul Lacaze, Kathlyn J Ronaldson, John J McNeil, Mahesh Jayaram, Naveen Thomas, Rory Sellmer, David N Crockford, Robert Stowe, Steven C Greenway, Christos Pantelis, Chad A Bousman1 module1 module 15 ml 3 modules2 x 100 1 module 5 G1 module1 module 1 kit(s) 1 module
#35314680 2022/03/21 To Up
Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion.Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A, CPT2, ACAD9 cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-ÎºB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.
Nian Jiang, Bowen Xie, Wenwu Xiao, Ming Fan, Shanxiu Xu, Yixin Duan, Yamah Hamsafar, Angela C Evans, Jie Huang, Weibing Zhou, Xuelei Lin, Ningrong Ye, Siyi Wanggou, Wen Chen, Di Jing, Ruben C Fragoso, Brittany N Dugger, Paul F Wilson, Matthew A Coleman, Shuli Xia, Xuejun Li, Lun-Quan Sun, Arta M Monjazeb, Aijun Wang, William J Murphy, Hsing-Jien Kung, Kit S Lam, Hong-Wu Chen, Jian Jian Li