Generation of a high power electron beam from a 2.6 MV vacuum field emission diode

Hwang, Chang‐Sing; Wu, M.W.; Hou, W.-S.; Li, S.H.; Yeh, Jau-Tyne

doi:10.1016/0168-9002(90)91345-c

Cited by 5 publications

(6 citation statements)

References 7 publications

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“…1) (7-9). Additionally, esterification of fatty acids to cholesterol is catalyzed by the ER transmembrane proteins ACAT1 (acyl-CoA: cholesterol acyltransferase 1) and ACAT2 (10). Neutral lipids are thought to be formed within specific domains of the ER called mitochondria-associated membranes (11,12).…”

Section: Enzymes For Neutral Lipid Synthesis Reside In Ermentioning

confidence: 99%

“…A major question is how a membrane-spanning protein with one or more luminal domains can localize to LDs, which lack an aqueous compartment. Both DGAT2 and ACAT2 have a single ER luminal domain that is rich in hydrophobic residues (10,14,15); it has been proposed that both the putative membrane-spanning and luminal sequences of DGAT2 may be embedded into lipid-filled cores of LDs. If this model is correct, then it would not be surprising to find ACAT2 on LDs; however, neither ACAT2 nor DGAT2 has been found in the proteomes of LDs isolated from a number of different cells, suggesting that these enzymes are embedded into membranes that are in close contact with LDs.…”

Section: Lds Peroxisomes and Mitochondria Contribute To Neutral Lipmentioning

confidence: 99%

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Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion

Brasaemle

Wolins

2012

Journal of Biological Chemistry

211

166

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Lipid droplets (LDs) are organelles found in most types of cells in the tissues of vertebrates, invertebrates, and plants, as well as in bacteria and yeast. They differ from other organelles in binding a unique complement of proteins and lacking an aqueous core but share aspects of protein trafficking with secretory membrane compartments. In this minireview, we focus on recent evidence supporting an endoplasmic reticulum origin for LD formation and discuss recent findings regarding LD maturation and fusion.Eukaryotic cells produce and traffic membranes that maintain intracellular compartments that facilitate regulation of metabolism by controlling the subcellular localization of metabolites, the concentrations of enzymes and substrates to optimize enzyme reactions, and the isolation of toxic metabolites. Fatty acids supply a major source of energy for organisms but also can be toxic. Cells escape cytotoxicity by esterifying fatty acids into neutral lipids and packaging them into lipid droplets (LDs) 3 coated with phospholipids and proteins. When cells are exposed to excess fatty acids, protein-coated LDs replete with neutral lipids bud from membranes of the endoplasmic reticulum (ER). When levels of exogenous fatty acids wane, the surface proteins of nascent LDs are exchanged for other proteins that serve various functions on mature LDs. Recent studies have established LDs as a distinct organelle.The protein components of LDs have been increasingly studied over the past decade. In chordates and flies, members of the perilipin family of proteins are among the most abundant proteins coating LDs (1, 2). Perilipins interact with both lipid and cytosolic proteins, forming an amphipathic interface between stored lipids and the cytosol. LDs in the cells of various vertebrate tissues are coated with two to four types of perilipin; each unique combination of perilipins imparts tissue-specific management of lipid metabolism. The expression of perilipin 1 is limited to adipocytes of white and brown adipose tissue and steroidogenic cells of the adrenal cortex, testes, and ovaries; moreover, subcellular localization of perilipin 1 is essentially restricted to LDs. Perilipin 2 (formerly adipophilin/ADRP (adipose differentiation-related protein)) and perilipin 3 (formerly TIP47 (tail-interacting protein of 47 kDa)) are ubiquitously expressed and hence contribute to the protein coat of LDs in the majority of cells. Perilipin 2 localizes primarily to LDs. Perilipin 3 is stable in the cytoplasm of cells but rapidly associates with nascent LDs when cells are incubated with fatty acids to promote triacylglycerol (TAG) synthesis and storage. Perilipin 4 (formerly S3-12) is expressed primarily in adipocytes of white adipose tissue and localizes to buds of nascent LDs along the ER. Perilipin 5 (formerly MLDP (myocardial lipid droplet protein)/OXPAT (oxidative protein of the PAT family)/LSDP5 (lipid storage droplet protein 5)) is expressed in oxidative tissues, including cardiac and skeletal muscle, and in brown adipocytes. In addition...

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Section: Enzymes For Neutral Lipid Synthesis Reside In Ermentioning

confidence: 99%

Section: Lds Peroxisomes and Mitochondria Contribute To Neutral Lipmentioning

confidence: 99%

Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion

Brasaemle

Wolins

2012

Journal of Biological Chemistry

211

166

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“…ACAT1 has been found in almost all types of cells, but ACAT2 is expressed primarily in the small intestine and hepatocytes. 212,213) ACAT1 has recently become of interest in AD research because inhibition of ACAT1 by pharmacological and genetic techniques appears to be a potential therapeutic target for AD by reducing amyloid pathology and improving cognitive impairment. 214,215) However, essentially all sterol in the adult brain is unesterified cholesterol.…”

Section: Lipid Metabolism and Admentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFunctions of the central nervous system (CNS) are performed mainly by neurons and glia-primarily astrocytes, microglia and oligodendrocytes. It has been thought for a long time that glia only passively support neurons, but we now know that glia actively attend to assist in neuronal functions like synaptogenesis and neurotransmission. 1) Although it was believed that ca. 90% of the cells in the brain are glia and the rest of cells are neurons, Azevedo et al. recently reported that the numbers of neurons and non-neuronal cells (glia) are close to equal in human adult brain.2) Brain is the most cholesterol-rich organ in the body, and cholesterol metabolism in the CNS is tightly regulated between neurons and glia. [3][4][5][6][7] Imbalances in the metabolism of lipids, especially cholesterol, are closely linked to the development of several neurodegenerative disorders such as Alzheimer's disease, 8,9) Niemann-Pick type C disease 10) and Smith-Lemli Opitz syndrome. 11,12) In this review the regulation of lipid metabolism and the roles of glial lipoproteins in the CNS will be discussed. LIPID HOMEOSTASIS IN THE CNSThe system of lipid metabolism and transport in the CNS is different from that in peripheral tissues because the CNS is segregated from the peripheral circulation by the blood-brain barrier (BBB).13) Although lipoprotein particles can cross the BBB in vivo in Drosophila, which has a functional BBB like that in vertebrates, 14) lipoproteins in the mouse, rat and human do not cross the BBB. Consequently, since labeled cholesterol peripherally administrated was not found in the CNS of mammals, 15,16) cholesterol in the CNS is derived from de novo synthesis inside of the CNS. Furthermore, in the plasma of subjects who had liver transplantation the genotype of apolipoprotein (apo) E was that of the donor, whereas the subjects retained the own apo E genotype in the cerebrospinal fluid (CSF).17) Moreover, lipoproteins in the CNS consist of only high density lipoprotein (HDL)-like particles in contrast to the circulation which contains very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL. It is known that the HDL-like particles in the CNS are secreted from glia (glial lipoproteins), mainly astrocytes and microglia, under normal conditions, [18][19][20] however lipoproteins can be secreted from neurons in vitro 21,22) and in vivo 23) under some specific conditions. Unesterified cholesterol is the major sterol in the adult brain, and small amounts of desmosterol and cholesteryl ester are also present. The majority (70-80%) of cholesterol in the adult brain is in myelin formed by oligodendrocytes. 24)Thus, the activity of cholesterol synthesis in the CNS is the highest during the myelinogenesis. After myelination, cholesterol synthesis continues at very low level in the CNS, and occurs mainly in astrocytes. 5,13,24) Neurons do not efficiently synthesize cholesterol and rely on external source of cholesterol from astrocytes, 25) so that neurons take up cholesterol as lipoproteins via ...

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“…10) SOAT1 and SOAT2 share extensive homology, but the topology of the protein domains is thought to be different. 1,5,8,9) These data implied that beauveriolides would bind to a homology domain in SOAT1 and SOAT2, but also that the environment wherein the binding site is located might be different for SOAT1 and SOAT2, e.g., inside or outside of the cell membrane. We have accomplished the total synthesis of beauveriolide III and determined the absolute configuration of the (3S,4S)-3-hydroxy-4-methyloctanoic acid (HMA) moiety.…”

mentioning

confidence: 94%

“…1) Since CE accumulation in plasma is closely related to artery plaque formation, SOAT inhibitors are expected to be therapeutic agents for atherosclerosis. 2,3) Recent molecular biological studies have revealed the existence of two different SOAT isozymes-SOAT1 and SOAT2-in mammals.…”

mentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Beauveriolide Analogues Bearing Photoreactive Amino Acids

et al. 2016

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Beauveriolides I and III, which are naturally occurring cyclodepsipeptides, have been reported to bind to sterol O-acyltransferase (SOAT), inhibiting its ability to synthesize cholesteryl esters. To facilitate an analysis of the binding site(s) of these compounds, we designed beauveriolide analogues 1a-d wherein the Leu or D-allo-Ile residue was replaced by photoreactive amino acids possessing methyldiazirine or trifluoromethyldiazirine in the side chains. The methyldiazirine moiety was installed by reaction of methyl ketones with liquid ammonia to provide imine intermediates, followed by treatment with hydroxylamine-O-sulfonic acid to provide the diaziridines. Subsequent oxidation gave methyldiazirines. In contrast, trifluoromethyldiazirine derivatives were prepared from trifluoromethyl ketones via the oxime intermediates, which were transformed into diaziridines. Subsequent oxidation afforded trifluoromethyldiazirines. The synthesized photoreactive amino acids 3a-d were coupled with 3-hydroxy-4-methyloctanoic acid 4 and dipeptide 5, followed by macrolactamization to provide beauveriolide analogues 1a-d. The SOAT inhibitory activities of 1a-d were found to be as potent as those of beauveriolides I and III. Moreover, 1a-d inhibited SOAT1 selectively rather than SOAT2, which was also consistent with the behavior of beauveriolides I and III. Key words beauveriolide; sterol O-acyltransferase; photoaffinity labeling; diazirineSterol O-acyltransferase (SOAT, also known as acylCoA : cholesterol acyltransferase (ACAT)) catalyzes conversion of cholesterol and long-chain fatty-acyl-CoA to cholesteryl esters (CE).1) Since CE accumulation in plasma is closely related to artery plaque formation, SOAT inhibitors are expected to be therapeutic agents for atherosclerosis.2,3) Recent molecular biological studies have revealed the existence of two different SOAT isozymes-SOAT1 and SOAT2-in mammals. 4-7)SOAT1 is ubiquitously expressed in most tissues and cells, including macrophages, and is related to foam cell formation. On the other hand, SOAT2, which is expressed predominantly in the liver and intestine, is related to food cholesterol absorption and secretion of low-density lipoprotein (LDL). Since SOAT1 and SOAT2 function differently, 8,9) isozyme selectivity is important for developing SOAT inhibitors. So far, a number of SOAT inhibitors have been reported and their isozyme selectivities have been discussed. 2,3,[10][11][12] Beauveriolides I and III (Fig. 1A), isolated from a culture broth of Beauveria sp. FO-6979, inhibit lipid droplet formation in mouse peritoneal macrophages.13,14) These cyclodepsipeptides were found to inhibit CE synthesis by blocking SOAT activity.15) Ohshiro et al. reported that beauveriolides I and III selectively inhibited SOAT1 in a cell-based assay using two Chinese hamster ovary (CHO) cell lines expressing African green monkey SOAT1 (SOAT1-CHO) and SOAT2 (SOAT2-CHO).10) However, beauveriolides I and III inhibit SOAT2 as well as SOAT1 in an enzyme assay using the microsomal fraction prepared from S...

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Generation of a high power electron beam from a 2.6 MV vacuum field emission diode

Cited by 5 publications

References 7 publications

Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion

Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Design, Synthesis, and Biological Evaluation of Beauveriolide Analogues Bearing Photoreactive Amino Acids

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