http://publicationslist.org/data/steve.meaney/atom.xml Steve Meaneyhttp://publicationslist.org/steve.meaney$basepathfavicon.icoRecent additions to Steve Meaney's PublicationsList.org pagehttp://publicationslist.org/publications.png2007-09-03T11:26:34Z http://publicationslist.org/steve.meaney/refid5 2007-08-30T15:42:33Z

Recently, we demonstrated a net blood-to-brain passage of the oxysterol 27-hydroxycholesterol corresponding to 4-5 mg/day. As the steady-state levels of this sterol are only 1-2 mug/g brain tissue, we hypothesized that it is metabolized and subsequently eliminated from the brain. To explore this concept, we first measured the capacity of in vitro systems representing the major cell populations fou...<br/><br/>Steve Meaney, Maura Heverin, Ute Panzenboeck, Lena Ekström, Magnus Axelsson, Ulla Andersson, Ulf Diczfalusy, Irina Pikuleva, John Wahren, Wolfgang Sattler, Ingemar Björkhem (2007) <i>J Lipid Res</i> <i></i> <i></i> 48: 4 944-951<br/>

http://publicationslist.org/steve.meaney/refid19 2007-09-03T11:25:45Z

OBJECTIVE: Characterization of cholesterol homeostasis in male mice with a genetic inactivation of 3beta-hydroxysteroid-Delta(24)-reductase, causing replacement of almost all cholesterol with desmosterol. METHODS AND RESULTS: There was an increase in hepatic sterol synthesis and markedly increased fecal loss of neutral sterols. Fecal excretion of bile acids was similar in knockout mice and in cont...<br/><br/> Heverin, Meaney, Brafman, Shafir, Olin, Shafaati, von Bahr, Larsson, Lövgren-Sandblom, Diczfalusy, Parini, Feinstein, Björkhem (2007) <i>Arterioscler Thromb Vasc Biol</i> : <br/>

http://publicationslist.org/steve.meaney/refid3 2007-08-30T15:42:33Z

The most serious consequence of sterol 27-hydroxylase deficiency in humans [cerebrotendinous xanthomatosis (CTX)] is the development of cholestanol-containing brain xanthomas. The cholestanol in the brain may be derived from the circulation or from 7alpha-hydroxylated intermediates in bile acid synthesis, present at 50- to 250-fold increased levels in plasma. Here, we demonstrate a transfer of 7al...<br/><br/>Ute Panzenboeck, Ulla Andersson, Magnus Hansson, Wolfgang Sattler, Steve Meaney, Ingemar Björkhem (2007) <i>J Lipid Res</i> <i></i> <i></i> 48: 5 1167-1174<br/>

http://publicationslist.org/steve.meaney/refid4 2007-08-30T15:42:33Z

Mevalonate kinase (MVK) catalyses an early step in cholesterol biosynthesis converting mevalonate to phosphomevalonate. Cob(I)alamin adenosyltransferase (MMAB) converts cob(I)alamin to adenosylcobalamin, functionally required for mitochondrial methylmalonyl-CoA mutase activity and succinyl-CoA formation. These two synthenic genes are found in a head-to-head formation on chromosome 12 in man and ch...<br/><br/>Charlotte Murphy, Ann Marie Murray, Steve Meaney, Mats Gåfvels (2007) <i>Biochem Biophys Res Commun</i> <i></i> <i></i> 355: 2 359-364<br/>

http://publicationslist.org/steve.meaney/refid1 2007-08-30T15:42:33Z

The cholesterol 24-hydroxylase encoded by the gene CYP46 is expressed almost exclusively in central nervous system (CNS) neurons and catalyzes the formation of 24S-hydroxycholesterol (24S-OHC) from cholesterol. This conversion corresponds to a major pathway for excretion of excess cholesterol from the brain. There is a significant flux of another oxysterol, 27-hydroxycholesterol (27-OHC) from the ...<br/><br/>D Famer, S Meaney, M Mousavi, A Nordberg, I Björkhem, M Crisby (2007) <i>Biochem Biophys Res Commun</i> <i></i> <i></i> 359: 1 46-50<br/>

http://publicationslist.org/steve.meaney/refid2 2007-08-30T15:42:33Z

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder believed to be exclusively caused by mutations in the CYP27A1 gene coding for the enzyme sterol 27-hydroxylase. Common findings in CTX are tendon xanthomas, cataracts and progressive neurological dysfunction. Here, we characterize an adult female patient with tendon xanthomas and classic biochemical findings of CTX (i.e. h...<br/><br/>M Hansson, M Olin, C-H Floren, S von Bahr, F van't Hooft, S Meaney, G Eggertsen, I Björkhem (2007) <i>J Intern Med</i> <i></i> <i></i> 261: 5 504-510<br/>

http://publicationslist.org/steve.meaney/refid7 2007-08-30T15:42:33Z

Mammalian CNS contains a disproportionally large and remarkably stable pool of cholesterol. Despite an efficient recycling there is some requirement for elimination of brain cholesterol. Conversion of cholesterol into 24S-hydroxycholesterol by the cholesterol 24-hydroxylase (CYP46A1) is the quantitatively most important mechanism. Based on the protein expression and plasma levels of 24S-hydroxycho...<br/><br/>Yoshihiko Ohyama, Steve Meaney, Maura Heverin, Lena Ekström, Anat Brafman, Millicent Shafir, Ulla Andersson, Maria Olin, Gösta Eggertsen, Ulf Diczfalusy, Elena Feinstein, Ingemar Björkhem (2006) <i>J Biol Chem</i> <i></i> <i></i> 281: 7 3810-3820<br/>

http://publicationslist.org/steve.meaney/refid6 2007-08-30T15:42:33Z

There is a clear link between cholesterol turnover and neurodegenerative diseases and hypercholesterolemia is an established risk factor for Alzheimer's disease (AD). The failure to demonstrate a transfer of cholesterol from the circulation into the brain in humans and experimental animals makes it difficult to explain the link between hypercholesterolemia and AD. In contrast to cholesterol itself...<br/><br/>I Björkhem, M Heverin, V Leoni, S Meaney, U Diczfalusy (2006) <i>Acta Neurol Scand Suppl</i> <i></i> <i></i> 185: 43-49<br/>

http://publicationslist.org/steve.meaney/refid9 2007-08-30T15:42:33Z

The liver X receptor (LXR)alpha and -beta has been found to play a central role in maintaining cellular cholesterol homeostasis. In this study we comprehensively investigated the effect of deleting LXRalpha and -beta on testicular morphology and function. In the absence of LXRbeta, excessive cholesterol accumulated in the Sertoli cells from 2.5 months, resulting in severe cellular disruption and d...<br/><br/>Kirsten M Robertson, Gertrud U Schuster, Knut R Steffensen, Outi Hovatta, Steve Meaney, Kjell Hultenby, Lisen C Johansson, Konstantin Svechnikov, Olle Söder, Jan-Ake Gustafsson (2005) <i>Endocrinology</i> <i></i> <i></i> 146: 6 2519-2530<br/>

http://publicationslist.org/steve.meaney/refid8 2007-08-30T15:42:33Z

Sterols are essential components of virtually all higher eukaryotic organisms, though the exact identity of the dominating sterol varies between species, from the C-27 of cholesterol in vertebrates to the C-28 and C-29 sterols of plants and invertebrates. In addition to their role as structural components of cell membranes these sterols are also converted into a variety of biologically active horm...<br/><br/>Steve Meaney (2005) <i>FASEB J</i> <i></i> <i></i> 19: 10 1220-1224<br/>

http://publicationslist.org/steve.meaney/refid10 2007-08-30T15:42:33Z

Side chain oxidized oxysterols have a unique ability to traverse lipophilic membranes. We tested the hypothesis that there is a net flux of 27-hydroxycholesterol from the circulation into the brain using plasma samples collected from the internal jugular vein and an artery of healthy male volunteers. Two independent studies were performed, one in which total levels of 27-hydroxycholesterol were me...<br/><br/>Maura Heverin, Steve Meaney, Dieter Lütjohann, Ulf Diczfalusy, John Wahren, Ingemar Björkhem (2005) <i>J Lipid Res</i> <i></i> <i></i> 46: 5 1047-1052<br/>

http://publicationslist.org/steve.meaney/refid12 2007-08-30T15:43:02Z

Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Approximately 25% of the total amount of the cholesterol present in humans is localized to this organ, most of it present in myelin. Almost all brain cholesterol is a product of local synthesis, with the blood-brain barrier ef...<br/><br/>Ingemar Björkhem, Steve Meaney (2004) <i>Arterioscler Thromb Vasc Biol</i> <i></i> <i></i> 24: 5 806-815<br/>

http://publicationslist.org/steve.meaney/refid11 2007-08-30T15:43:02Z

The conversion of cholesterol into the more polar metabolites 27-hydroxycholesterol (27-OH) and cholestenoic acid by the cytochrome P450 sterol 27-hydroxylase is a cholesterol-removal mechanism used by almost all cells. Most of the cholestenoic acid present in the circulation originates from the lung, and it has been suggested that sterol 27-hydroxylase is of particular importance for cholesterol ...<br/><br/>Steve Meaney, Tracey L Bonfield, Magnus Hansson, Amir Babiker, Mani S Kavuru, Mary Jane Thomassen (2004) <i>J Lipid Res</i> <i></i> <i></i> 45: 12 2354-2360<br/>

http://publicationslist.org/steve.meaney/refid14 2007-08-30T15:43:02Z

The side chain oxidized oxysterol 24S-hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain and about 2 in the circulation. This ratio...<br/><br/>Valerio Leoni, Thomas Masterman, Pria Patel, Steve Meaney, Ulf Diczfalusy, Ingemar Björkhem (2003) <i>J Lipid Res</i> <i></i> <i></i> 44: 4 793-799<br/>

http://publicationslist.org/steve.meaney/refid13 2007-08-30T15:43:02Z

3 Beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha-dihydroxy-5-cholestenoic acid, and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid are metabolites of cholesterol present at significant concentrations (40-80 ng/ml) in human circulation. The 7 alpha-hydroxylated acids may be formed from cholesterol via two major pathways initiated by oxidations at either the 7 alpha- or 27-positions. In an attempt to c...<br/><br/>Steve Meaney, Amir Babiker, Dieter Lütjohann, Ulf Diczfalusy, Magnus Axelson, Ingemar Björkhem (2003) <i>Steroids</i> <i></i> <i></i> 68: 7-8 595-601<br/>

http://publicationslist.org/steve.meaney/refid16 2007-08-30T15:43:03Z

Oxysterols are oxygenated derivatives of cholesterol that are intermediates in cholesterol excretion pathways. They may also be regarded as transport forms of cholesterol and introduction of an additional hydroxyl group facilitates flux of cholesterol across cell membranes and the blood-brain barrier. According to current concepts, oxysterols are also mediating a number of cholesterol-induced meta...<br/><br/>Ingemar Björkhem, Steve Meaney, Ulf Diczfalusy (2002) <i>Curr Opin Lipidol</i> <i></i> <i></i> 13: 3 247-253<br/>

http://publicationslist.org/steve.meaney/refid15 2007-08-30T15:43:03Z

Oxysterols possess powerful biological activities. Some of their effects on the regulation of key enzymes are similar to those of cholesterol, but are much more potent. One of the critical properties of oxysterols is their ability to pass lipophilic membranes at a high rate. Transfer of unesterified 25-hydroxycholesterol from red blood cells to plasma has been reported to occur more than 1,000 tim...<br/><br/>Steve Meaney, Karl Bodin, Ulf Diczfalusy, Ingemar Björkhem (2002) <i>J Lipid Res</i> <i></i> <i></i> 43: 12 2130-2135<br/>

http://publicationslist.org/steve.meaney/refid17 2007-08-30T15:43:03Z

The major oxysterols in human circulation are 7 alpha-, 27-, and (24S)-hydroxycholesterol. Two unique experiments were performed to elucidate their origin and kinetics. A volunteer was exposed to (18)O(2)-enriched air. A rapid incorporation of (18)O in both 7 alpha- and 27-hydroxycholesterol and disappearance of label after exposure were observed. The half-life was estimated to be less than 1 h. I...<br/><br/>S Meaney, M Hassan, A Sakinis, D Lütjohann, K von Bergmann, A Wennmalm , U Diczfalusy, I Björkhem (2001) <i>J Lipid Res</i> <i></i> <i></i> 42: 1 70-78<br/>

http://publicationslist.org/steve.meaney/refid18 2007-08-30T15:43:03Z

In order to study the origin of different oxysterols in the circulation, in particular 24S-hydroxycholesterol, different pools of cholesterol in rat and mouse were labelled by feeding the animals with a diet supplemented with 0.3 or 0.5% hexadeuterium-labelled cholesterol, respectively, for 10 days. The incorporation of deuterium label in cholesterol and different oxysterols was measured by combin...<br/><br/>S Meaney, D Lütjohann, U Diczfalusy, I Björkhem (2000) <i>Biochim Biophys Acta</i> <i></i> <i></i> 1486: 2-3 293-298<br/>