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https://www.readbyqxmd.com/read/28807695/doxorubicin-enhance-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#1
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
August 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28801370/impact-of-tlr-2-tlr-4-activation-on-the-expression-of-abca1-and-abcg1-in-raw-cells
#2
Kana Suzuki, Yasushi Kawakami, Kazuyoshi Yamauchi
Toll-like receptors (TLR) activation is thought to modulate the macrophage cholesterol efflux and contribute to the atherosclerosis progression; however, the precise pathophysiological mechanism remains unclear. We investigated the effects of TLR2- and TLR4-activation on the expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 in a mouse macrophage cell line, Raw 264.7. Both TLR2- and TLR4-activation upregulated the expression of ABCA1 mRNA but downregulated that of ABCG1 mRNA. These alterations may be mainly regulated by the following 3 cascades: (1) the TLR/myeloid differentiation primary-response protein 88/Liver X receptor pathway, which upregulated the ABCA1 mRNA; (2) NF-κB pathway, which downregulated the ABCG1 mRNA, and (3) the p38 pathway, which upregulated and stabilized ABCA1 mRNA...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28791414/tetramethylpyrazine-suppresses-lipid-accumulation-in-macrophages-via-upregulation-of-the-atp-binding-cassette-transporters-and-downregulation-of-scavenger-receptors
#3
Jie Duan, Dong Xiang, Hongli Luo, Guojun Wang, Yun Ye, Chao Yu, Xiuying Li
Tetramethylpyrazine (TMP), a biologically active ingredient first extracted from the Chinese medicinal plant Ligusticum wallichii Franchat., has athero-protective activity, yet the particular mechanisms have not been completely explored. The present study was designed to investigate the effect of TMP and its possible mechanisms in RAW264.7 macrophages and apolipoprotein E-deficient (ApoE-/-) mice. TMP treatment markedly increased the cholesterol efflux and inhibited oxidized low-density lipoprotein (ox-LDL) uptake, thus, ameliorating lipid accumulation in macrophages...
August 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28775237/c1q-tumor-necrosis-factor-related-protein-3-protects-macrophages-against-lps-induced-lipid-accumulation-inflammation-and-phenotype-transition-via-ppar%C3%AE-and-tlr4-mediated-pathways
#4
Jiale Lin, Qi Liu, Hui Zhang, Xingtao Huang, Ruoxi Zhang, Shuyuan Chen, Xuedong Wang, Bo Yu, Jingbo Hou
Macrophage inflammation and foam cell formation are critical events during the initiation and development of atherosclerosis (AS). C1q/tumor necrosis factor-related protein-3 (CTRP3) is a novel adipokine with anti-inflammatory and cardioprotection properties; however, little is known regarding the influence of CTRP3 on AS. As macrophages play a key role in AS, this study investigated the effects of CTRP3 on macrophage lipid metabolism, inflammatory reactions, and phenotype transition, as well as underlying mechanisms, to reveal the relationship between CTRP3 and AS...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28768900/plasminogen-promotes-cholesterol-efflux-by-the-abca1-pathway
#5
Nathalie Pamir, Patrick M Hutchins, Graziella E Ronsein, Hao Wei, Chongren Tang, Riku Das, Tomas Vaisar, Edward Plow, Volker Schuster, Catherine A Reardon, Richard Weinberg, David A Dichek, Santica Marcovina, Godfrey S Getz, Jay W Heinecke
Using genetic and biochemical approaches, we investigated proteins that regulate macrophage cholesterol efflux capacity (CEC) and ABCA1-specific CEC (ABCA1 CEC), 2 functional assays that predict cardiovascular disease (CVD). Macrophage CEC and the concentration of HDL particles were markedly reduced in mice deficient in apolipoprotein A-I (APOA1) or apolipoprotein E (APOE) but not apolipoprotein A-IV (APOA4). ABCA1 CEC was markedly reduced in APOA1-deficient mice but was barely affected in mice deficient in APOE or APOA4...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28767713/apolipoprotein-a-i-exchange-is-impaired-in-metabolic-syndrome-patients-asymptomatic-for-diabetes-and-cardiovascular-disease
#6
Mark S Borja, Bradley Hammerson, Chongren Tang, Olga V Savinova, Gregory C Shearer, Michael N Oda
OBJECTIVE: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. METHODS: HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28767201/the-apolipoprotein-a-i-mimetic-peptide-d-4f-restrains-neointimal-formation-through-heme-oxygenase-1-up-regulation
#7
Donghui Liu, Mengzhang Wu, Qian Du, Zhenzhen Ding, Mingming Qian, Zijia Tong, Wenqi Xu, Le Zhang, He Chang, Yan Wang, Caihua Huang, Donghai Lin
D-4F, an apolipoprotein A-I (apoA-I) mimetic peptide, possesses distinctly anti-atherogenic effects. However, the biological functions and mechanisms of D-4F on the hyperplasia of vascular smooth muscle cells (VSMCs) remain unclear. This study aimed to determine its roles in the proliferation and migration of VSMCs. In vitro, D-4F inhibited VSMC proliferation and migration induced by ox-LDL in a dose-dependent manner. D-4F up-regulated heme oxygenase-1 (HO-1) expression in VSMCs, and the PI3K/Akt/AMP-activated protein kinase (AMPK) pathway was involved in these processes...
August 2, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28766509/high-density-lipoprotein-metabolism-and-reverse-cholesterol-transport-strategies-for-raising-hdl-cholesterol
#8
Katerina Tosheska Trajkovska, Sonja Topuzovska
A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge...
August 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28760679/amelioration-of-amyloid-%C3%AE-induced-retinal-inflammatory-responses-by-a-lxr-agonist-to901317-is-associated-with-inhibition-of-the-nf-%C3%AE%C2%BAb-signaling-and-nlrp3-inflammasome
#9
Chunyan Lei, Ru Lin, Jiaming Wang, Lifei Tao, Xinyu Fu, Yiguo Qiu, Bo Lei
Amyloid β (Aβ) is a pathogenic peptide associated with many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The retinal inflammation in response to Aβ is implicated in the pathogenesis of several ocular diseases including age-related macular degeneration, Alzheimer's-related optic neuropathy and glaucoma. In the present study, we found that a single intravitreal injection of oligomeric Aβ1-40 in mouse activated the NLRP3 inflammasome and the NF-κB signaling, induced the production of inflammatory cytokines including TNF-α and IL-6...
July 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28742600/cholesterol-reduction-and-macrophage-function-role-of-paraoxonases
#10
C Roger White, G M Anantharamaiah
PURPOSE OF REVIEW: Unregulated uptake of oxidized LDL by macrophages to form foam cells is the hallmark for atherosclerosis. The paraoxonase (PON) family of enzymes plays a critical role in attenuating atherosclerotic lesion formation by hydrolyzing lipid peroxides (LOOHs) and preventing the oxidation of LDL particles and by enhancing HDL-mediated cholesterol efflux. Findings in recent years suggest novel mechanisms by which PON isoforms interact with macrophages to regulate cholesterol metabolism and cellular function...
July 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28741954/side-chain-modified-ergosterol-and-stigmasterol-derivatives-as-liver-x-receptor-agonists
#11
Maura Marinozzi, Francisco Fermin Castro Navas, Daniela Maggioni, Emanuele Carosati, Giovanni Bocci, Maria Carloncelli, Gianluca Giorgi, Gabriele Cruciani, Raffaella Fontana, Vincenzo Russo
A series of stigmasterol and ergosterol derivatives, characterized by the presence of oxygenated functions at C-22 and/or C-23 positions, were designed as potential liver X receptor (LXR) agonists. The absolute configuration of the newly created chiral centers was definitively assigned for all the corresponding compounds. Among the 16 synthesized compounds, 21, 27, and 28 were found to be selective LXRα agonists, whereas 20, 22, and 25 showed good selectivity for the LXRβ isoform. In particular, 25 showed the same degree of potency as 22R-HC (3) at LXRβ, while it was virtually inactive at LXRα (EC50 = 14...
July 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28739279/eicosapentaenoic-acid-membrane-incorporation-impairs-cholesterol-efflux-from-cholesterol-loaded-human-macrophages-by-reducing-the-cholesteryl-ester-mobilization-from-lipid-droplets
#12
Natalie Fournier, Guillaume Sayet, Benoît Vedie, Maxime Nowak, Fatima Allaoui, Audrey Solgadi, Eric Caudron, Pierre Chaminade, Jean-François Benoist, Jean-Louis Paul
A diet containing a high n-3/n-6 polyunsaturated fatty acids (PUFA) ratio has cardioprotective properties. PUFAs incorporation into membranes influences the function of membrane proteins. We investigated the impact of the membrane incorporation of PUFAs, especially eicosapentaenoic acid (EPA) (C20:5 n-3), on the anti-atherogenic cholesterol efflux pathways. We used cholesteryl esters (CE)-loaded human monocyte-derived macrophages (HMDM) to mimic foam cells exposed to the FAs for a long period of time to ensure their incorporation into cellular membranes...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28737726/synthesis-and-biological-evaluation-of-ginsenoside-compound-k-derivatives-as-a-novel-class-of-lxr%C3%AE-activator
#13
Yan Huang, Hongmei Liu, Yingxian Zhang, Jin Li, Chenping Wang, Li Zhou, Yi Jia, Xiaohui Li
Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41...
July 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28726269/previous-physical-exercise-alters-the-hepatic-profile-of-oxidative-inflammatory-status-and-limits-the-secondary-brain-damage-induced-by-severe-traumatic-brain-injury-in-rats
#14
Mauro Robson Torres de Castro, Ana Paula de Oliveira Ferreira, Guilherme Lago Busanello, Luís Roberto Hart da Silva, Mauro Eduardo Porto da Silveira Junior, Fernando da Silva Fiorin, Gabriela Arrifano, Maria Elena Crespo-López, Rômulo Pillon Barcelos, María J Cuevas, Guilherme Bresciani, Javier González-Gallego, Michele Rechia Fighera, Luiz Fernando Freire Royes
KEY POINTS: An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs...
July 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28725889/cholesterol-lowering-by-pediococcus-acidilactici-lab4-and-lactobacillus-plantarum-lab12-in-adult-zebrafish-is-associated-with-improved-memory-and-involves-an-interplay-between-npc1l1-and-abca1
#15
Fei Tieng Lim, Siong Meng Lim, Kalavathy Ramasamy
This study assessed the cholesterol lowering effect of Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 using adult zebrafish. Animals were fed with a high cholesterol diet (HCD) with/without LAB for seven weeks. Serum and liver cholesterol was quantified using colorimetric and dye staining methods. Expressions of npc1l1 and abca1 in the liver and intestine and appa in the brain were quantified using RT-PCR. Serum and liver cholesterol was significantly lowered in LAB4- and LAB12-fed zebrafish (≤64% and ≤71%, respectively), with reduced liver cholesterol deposition...
August 1, 2017: Food & Function
https://www.readbyqxmd.com/read/28710789/atr-101-inhibits-cholesterol-efflux-and-cortisol-secretion-by-abc-transporters-causing-cytotoxic-cholesterol-accumulation-in-adrenocortical-carcinoma-cells
#16
Veronica Elizabeth Burns, Tom Klaus Kerppola
BACKGROUND AND PURPOSE: To further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR-101 (PD132301-02). EXPERIMENTAL APPROACH: We compared the effects of ATR-101, PD129337, and ABC transporter inhibitors, on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC-derived cell lines...
July 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28706492/lower-expression-of-slc27a1-enhances-intramuscular-fat-deposition-in-chicken-via-down-regulated-fatty-acid-oxidation-mediated-by-cpt1a
#17
Fengfang Qiu, Liang Xie, Jing-E Ma, Wen Luo, Li Zhang, Zhe Chao, Shaohao Chen, Qinghua Nie, Zhemin Lin, Xiquan Zhang
Intramuscular fat (IMF) is recognized as the predominant factor affecting meat quality due to its positive correlation with tenderness, juiciness, and flavor. Chicken IMF deposition depends on the balance among lipid synthesis, transport, uptake, and subsequent metabolism, involving a lot of genes and pathways, however, its precise molecular mechanisms remain poorly understood. In the present study, the breast muscle tissue of female Wenchang chickens (WC) (higher IMF content, 1.24 in D120 and 1.62 in D180) and female White Recessive Rock chickens (WRR; lower IMF content, 0...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28704619/advanced-glycation-end-products-affect-cholesterol-homeostasis-by-impairing-abca1-expression-on-macrophages
#18
Olivier Kamtchueng Simo, Souade Ikhlef, Hicham Berrougui, Abdelouahed Khalil
Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice...
August 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28701354/pleiotropic-effects-of-apolipoprotein-c3-on-hdl-functionality-and-adipose-tissue-metabolic-activity
#19
Evangelia Zvintzou, Marie Lhomme, Stella Chasapi, Serafoula Filou, Vassilis Theodoropoulos, Eva Xepapadaki, Anatol Kontush, George Spyroulias, Constantinos C Tellis, Alexandros D Tselepis, Caterina Constantinou, Kyriakos E Kypreos
Apolipoprotein C3 (APOC3) is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to pre-existing particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis, by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype...
July 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28700834/petroleum-ether-extract-of-njavara-rice-bran-upregulates-jak2-stat3-mediated-anti-inflammatory-profile-in-macrophages-and-aortic-endothelial-cells-promoting-regression-of-atherosclerosis
#20
Chithra K Pushpan, Jayalekshmy Ananthasankaran, Helen Antony
"Njavara"(Oryza sativa Linn) is a unique rice variety grown in Kerala that is reported to have significantly higher antioxidant, anti-inflammatory, chemical indices, and bioactive components compared with staple rice varieties. However, the role of NBE in reversing the atherosclerosis development remains unclear. The present study aimed to elucidate the role of Njavara rice bran petroleum ether extract (NBE) in promoting atherosclerotic regression. Male New Zealand white breed rabbits were divided into three groups...
July 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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