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Akira Katsube, Hisamitsu Hayashi, Hiroyuki Kusuhara
OBJECTIVE: ATP-binding cassette transporter A1 (ABCA1) exerts an atheroprotective action through the biogenesis of high-density lipoprotein in hepatocytes and prevents the formation of foam cells from macrophages. Controlling ABCA1 is a rational approach to improving atherosclerotic cardiovascular disease. Although much is known about the regulatory mechanism of ABCA1 synthesis, the molecular mechanism underpinning its degradation remains to be clearly described. APPROACH AND RESULTS: ABCA1 possesses potential sites of phosphorylation by serine/threonine-protein kinase Pim-1 (Pim-1)...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Corneille Edgar Ontsouka, Xiao Huang, Eldar Aliyev, Christiane Albrecht
Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport activates signaling pathways, and how lactogenic hormones regulate it. To clarify these aspects, lipid transport and expressional analyses were performed in bovine primary (bMEC) and/or immortalized (MAC-T) MEC cultures...
October 16, 2016: Molecular and Cellular Endocrinology
Nigora Mukhamedova, Anh Hoang, Huanhuan L Cui, Irena Carmichael, Ying Fu, Michael Bukrinsky, Dmitri Sviridov
OBJECTIVE: ABCA1 (ATP-binding cassette transporter A1) is the principal protein responsible for cellular cholesterol efflux. Abundance and functionality of ABCA1 is regulated both transcriptionally and post-translationally, with endocytosis of ABCA1 being an important element of post-translational regulation. Functional ABCA1 resides on the plasma membrane but can be internalized and either degraded or recycled back to the plasma membrane. The interaction between the degradative and recycling pathways determines the abundance of ABCA1 and may contribute to the efflux of intracellular cholesterol...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Xueting Jin, Denis Sviridov, Ying Liu, Boris Vaisman, Lia Addadi, Alan T Remaley, Howard S Kruth
OBJECTIVE: We examined the function of ABCA1 (ATP-binding cassette transporter A1) in ApoA-I (apolipoprotein A-I) mobilization of cholesterol microdomains deposited into the extracellular matrix by cholesterol-enriched macrophages. We have also determined whether an ApoA-I mimetic peptide without and with complexing to sphingomyelin can mobilize macrophage-deposited cholesterol microdomains. APPROACH AND RESULTS: Extracellular cholesterol microdomains deposited by cholesterol-enriched macrophages were detected with a monoclonal antibody, 58B1...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Carrie J Finno, Matthew H Bordbari, Stephanie J Valberg, David Lee, Josi Herron, Kelly Hines, Tamer Monsour, Erica Scott, Danika L Bannasch, James Mickelson, Libin Xu
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord...
October 14, 2016: Free Radical Biology & Medicine
Tiantian Luo, Jing Hu, Dan Xi, Haowei Xiong, Wenshuai He, Jichen Liu, Menghao Li, Hao Lu, Jinzhen Zhao, Wenyan Lai, Zhigang Guo
Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4(+) T cells...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Y Lu, Y-P Jia
OBJECTIVE: Quercetin has been reported to have the activities of antioxidant, anti-inflammatory, anti-virus, anti-cancer and so on. Many studies showed that quercetin could lower blood pressure and improve blood capillary elasticity, and it can also reduce LDL oxidation and prevent atherosclerosis. Although quercetin has been recognized to have the function of preventing atherosclerosis, little is known about its underlying mechanism. In this study, we try to explore whether quercetin up-regulates LXRa-mediated ABCA1 expression...
September 2016: European Review for Medical and Pharmacological Sciences
Mohor B Sengupta, Suparna Saha, Pradeep K Mohanty, Kiran K Mukhopadhyay, Debashis Mukhopadhyay
ApoA1 is a player in reverse cholesterol transport that initiates multiple cellular pathways on binding to its receptor ABCA1. Its relation to neuronal injury is however unclear. We found ApoA1 to be increasingly abundant at a later time point in the secondary phase of traumatic spinal cord injury. In a cellular injury model of neuroblastoma, ApoA1 showed an initial diminished expression after infliction of injury, which sharply increased thereafter. Subsequently, ApoA1 was shown to alter wound healing dynamics in neuroblastoma injury model...
October 13, 2016: Molecular and Cellular Biochemistry
Adam M Speen, Hye-Young H Kim, Rebecca N Bauer, Megan Meyer, Kymberly M Gowdy, Michael B Fessler, Kelly E Duncan, Wei Liu, Ned A Porter, Ilona Jaspers
When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and β (α-EpCh, β-EpCh) and Secosterol A and B (Seco A, SecoB), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species...
October 4, 2016: Journal of Biological Chemistry
Blake J Cochran, Liming Hou, Anil Paul Chirackal Manavalan, Benjamin M Moore, Fatiha Tabet, Afroza Sultana, Luisa Cuesta Torres, Shudi Tang, Sudichhya Shrestha, Praween Senanayake, Mili Patel, William J Ryder, Andre Bongers, Marie Maraninchi, Valerie C Wasinger, Marit Westerterp, Alan R Tall, Philip J Barter, Kerry-Anne Rye
Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high glucose conditions and glucose disposal was shifted from skeletal muscle to adipose tissue...
October 4, 2016: Diabetes
Adam Ceroi, David Masson, Anne Roggy, Christophe Roumier, Cécile Chagué, Thierry Gauthier, Laure Philippe, Baptiste Lamarthée, Fanny Angelot-Delettre, Francis Bonnefoy, Sylvain Perruche, Sabeha Biichle, Claude Preudhomme, Elisabeth Macintyre, Laurent Lagrost, Francine Garnache-Ottou, Philippe Saas
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from plasmacytoid dendritic cells (PDC). No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared to those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDC. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes...
October 4, 2016: Blood
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
Kannadasan AnandBabu, S R Bharathidevi, Sarangapani Sripriya, Parveen Sen, Vadivelu Jaya Prakash, Appukuttan Bindu, Natarajan Viswanathan, Narayanasamy Angayarkanni
Age-related Macular Degeneration (AMD) is a multifactorial disease causing visual impairment in old age. Oxidative stress is one of the main contributors for the disease progression. Paraoxonase (PON), a HDL-resident antioxidant enzyme which removes oxidized low density lipoprotein (oxLDL), which is not studied much in AMD. This study assesses the PON activities in relation to the lipid status and genetic variants in AMD patients. In this prospective case-control study, a total of 48 AMD patients and 30 unrelated healthy controls were recruited...
September 28, 2016: Experimental Eye Research
Sayaka Nomura, Kaori Endo-Umeda, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa
Liver X receptor (LXR) agonists are candidates for the treatment of atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression, which contributes to reverse cholesterol transport (RCT) and to cholesterol efflux from the liver and intestine. However, LXR agonists also induce genes involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable increase in plasma and hepatic triglyceride (TG) levels...
September 30, 2016: ChemMedChem
Julian C van Capelleveen, John J P Kastelein, Aeilko H Zwinderman, Sander J H van Deventer, Heidi L Collins, Steven J Adelman, Patrick Round, John Ford, Daniel J Rader, G Kees Hovingh
BACKGROUND: TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. OBJECTIVE: To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non-ABCA1-driven CEC and on HDL particle distribution. METHODS: Total, non-ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215)...
September 2016: Journal of Clinical Lipidology
Bo Wang, Ping-Ping He, Gao-Feng Zeng, Tao Zhang, Xin-Ping Ou Yang
Previous studies have shown that miR-467b plays a central role in the progression of atherosclerosis via regulating LPL expression. However, the regulatory mechanism of miR-467b in regulateing the CE and FC formation is still unclear. Interestingly, computational analysis demonstrated that ACAT1 which converts intracellular FC into the storage form of CE, and ABCA1 which promotes cellular FC efflux may be target gene of miR-467b. Here, we examined whether miR-467b could target ACAT1 and ABCA1, thereby affecting the CE and FC formation in oxLDL-treatment RAW 264...
September 24, 2016: Biochimie
Duyen Quach, Cecilia Vitali, Fiona M La, Angel X Xiao, John S Millar, Chongren Tang, Daniel J Rader, Michael C Phillips, Nicholas N Lyssenko
ATP-binding cassette transporter A1 (ABCA1) mediates formation of disc-shaped high-density lipoprotein (HDL) from cell lipid and lipid-free apolipoprotein A-I (apo A-I). Discoidal HDL particles are heterogeneous in physicochemical characteristics for reasons that are understood incompletely. Discoidal lipoprotein particles similar in characteristics and heterogeneity to cell-formed discoidal HDL can be reconstituted from purified lipids and apo A-I by cell-free, physicochemical methods. The heterogeneity of reconstituted HDL (rHDL) is sensitive to the lipid composition of the starting lipid/apo A-I mixture...
September 24, 2016: Biochimica et Biophysica Acta
Soo Hwan Kim, Gi Jin Kim, Tsukuru Umemura, Seung Gwan Lee, Kyung Jin Cho
In order to investigate whether plasma microRNA-33a (miR-33a) can be a biomarker for the early detection of atherosclerosis and to reexamine the assumption that miR-33a represses the expression of ABCA1, we compared the expression levels of miR-33a and ATP-binding cassette A1 (ABCA1) using human plasma and supernatants of macrophage cultured media. We first separated ample number of plasma samples from left-over whole blood samples based on the criteria for normal or dyslipidemia, and stored them at -20 °C until use...
September 23, 2016: Molecular Biology Reports
Yoshihiro Kamada, Sachiho Kida, Ken-Ichi Hirano, Satoshi Yamaguchi, Akira Suzuki, Chikako Hashimoto, Akihiro Kimura, Motoya Sato, Hironobu Fujii, Tomoaki Sobajima, Akiko Yamamoto, Yusuke Ebisutani, Shinji Takamatsu, Shinichiro Shinzaki, Yuichi Yoshida, Makoto Yamada, Hironori Nagasaka, Tetsuo Takehara, Eiji Miyoshi
Glycosylation is involved in various pathophysiological conditions. N-Acetylglucosaminyltransferase V (GnT-V), catalyzing β1-6 branching in asparagines-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on high-density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants...
September 22, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jonathan Y Huang, Amelia R Gavin, Thomas S Richardson, Ali Rowhani-Rahbar, David S Siscovick, Hagit Hochner, Yechiel Friedlander, Daniel A Enquobahrie
Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007-2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes (ABCA1, INS-IGF2, LEP, HSD11B2, and NR3C1)...
October 1, 2016: American Journal of Epidemiology
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