Molecular species of glycerophospholipids and sphingomyelins of human plasma: Comparison to red blood cells

Myher, J. J.; Kuksis, A.; Pind, Steven

doi:10.1007/bf02535148

Cited by 111 publications

(71 citation statements)

References 25 publications

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“…After digestion (2 h, 30°C) of the phospholipids with phospholipase C, tridecanoin (20 ng) was added as an internal standard, and lipids were extracted. The mass of TG, cholesterol, and cholesteryl ester was determined by gas-liquid chromatography (28).…”

Section: Methodsmentioning

confidence: 99%

Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins

Jacobs

Devlin

Tabas

et al. 2004

Journal of Biological Chemistry

160

176

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CTP:phosphocholine cytidylyltransferase (CT) is the key regulatory enzyme in the CDP-choline pathway for the biosynthesis of phosphatidylcholine. Hepatic cells express both an ␣ and a ␤2 isoform of CT and can also synthesize phosphatidylcholine via the sequential methylation of phosphatidylethanolamine catalyzed by phosphatidylethanolamine N-methyltransferase. To ascertain the functional importance of CT␣, we created a mouse in which the hepatic CT␣ gene was specifically inactivated by the Cre/LoxP procedure. In CT␣ knockout mice, hepatic CT activity (due to residual CT␤2 activity as well as activity in nonhepatic cells) was 15% of normal, whereas phosphatidylethanolamine N-methyltransferase activity was elevated 2-fold compared with controls. Lipid analyses of the liver indicated that female knockout mice had reduced phosphatidylcholine levels and accumulated triacylglycerols. The plasma phosphatidylcholine concentration was reduced in the CT␣ knockout (independent of gender), as were levels of high density lipoproteins (cholesterol and apoAI) and very low density lipoproteins (triacylglycerols and apoB100). Experiments in which mice were injected with Triton WR1339 indicated that apoB secretion was decreased in hepatic-specific CT␣ knockout mice compared with controls. These results suggest an important role for hepatic CT␣ in regulating both hepatic and systemic lipid and lipoprotein metabolism.

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Section: Methodsmentioning

confidence: 99%

Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins

Jacobs

Devlin

Tabas

et al. 2004

Journal of Biological Chemistry

160

176

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“…After adding tridecanoin (20 ng) as an internal standard, lipids were extracted and the masses of cholesterol, cholesterol ester, and triacylglycerol were determined by gas-liquid chromatography (27).…”

Section: Construction Of a High Resolution Genetic Cross And Positionalmentioning

confidence: 99%

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

Sher

Aoyama

Huebsch

et al. 2006

Journal of Biological Chemistry

107

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Muscular dystrophies include a diverse group of genetically heterogeneous disorders that together affect 1 in 2000 births worldwide. The diseases are characterized by progressive muscle weakness and wasting that lead to severe disability and often premature death. Rostrocaudal muscular dystrophy (rmd) is a new recessive mouse mutation that causes a rapidly progressive muscular dystrophy and a neonatal forelimb bone deformity. The rmd mutation is a 1.6-kb intragenic deletion within the choline kinase beta (Chkb) gene, resulting in a complete loss of CHKB protein and enzymatic activity. CHKB is one of two mammalian choline kinase (CHK) enzymes (␣ and ␤) that catalyze the phosphorylation of choline to phosphocholine in the biosynthesis of the major membrane phospholipid phosphatidylcholine. While mutant rmd mice show a dramatic decrease of CHK activity in all tissues, the dystrophy is only evident in skeletal muscle tissues in an unusual rostral-to-caudal gradient. Minor membrane disruption similar to dysferlinopathies suggest that membrane fusion defects may underlie this dystrophy, because severe membrane disruptions are not evident as determined by creatine kinase levels, Evans Blue infiltration, and unaltered levels of proteins in the dystrophin-glycoprotein complex. The rmd mutant mouse offers the first demonstration of a defect in a phospholipid biosynthetic enzyme causing muscular dystrophy, representing a unique model for understanding mechanisms of muscle degeneration.Muscular dystrophies are a variable class of more than 20 human disorders characterized by progressive muscle wasting and weakness resulting from myofiber degeneration and regeneration. Histologically, variation in myofiber size with centrally localized nuclei, fibrosis, and fatty infiltration are common features (1, 2). Despite their common pathologies, the genetic causes, severity, age of onset, and inheritance patterns vary widely among the dystrophies. The Muscular Dystrophy Association currently lists over 40 neuromuscular diseases as targets for its research programs and categorizes them by phenotypic characteristics such as age of onset, affected muscle groups, and inheritance pattern (Muscular Dystrophy Association, www.mdausa.org). In the last 10 years, the genetic mapping and identification of novel skeletal muscle genes, including cytoskeletal, cytosolic, nuclear membrane, sarcolemmal and extracellular matrix proteins, has dramatically changed this phenotype-based classification and provided clues as to the molecular basis of these disorders (3). What was once considered a single disease entity such as limb-girdle muscular dystrophy (LGMD) 4 has now been subdivided into seven different molecularly defined autosomal dominant (LGMD1A-1G) and ten autosomal recessive (LGMD2A-2J) diseases. Not surprisingly, many of these genes have converged to define pathways critical for the normal functioning and maintenance of skeletal muscles. The fact that many muscular dystrophy cases exist in which mutations to known dystrophy-causing genes have...

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“…Polar head groups of phospholipids were digested by phospholipase C (Myher et al, 1989) and free hydroxyl moieties in lipids were derivatized with Sylon BFT (Supelco, Bellefonte, PA). Lipid species were analyzed and quantified by gas chromatography (Agilent Technologies, Wilmington, DE; 6890 Series equipped with a flame ionization detector).…”

Section: Lipid Analysismentioning

confidence: 99%

Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p Requirement

Tedrick

Trischuk

Lehner

et al. 2004

MBoC

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Organization of lipids into membrane microdomains is a vital mechanism of protein processing. Here we show that overexpression of ERG6, a gene involved in ergosterol synthesis, elevates sterol levels 1.5-fold on the vacuole membrane and enhances their homotypic fusion. The mechanism of sterol-enhanced fusion is not via more efficient sorting, but instead promotes increased kinetics of fusion subreactions. We initially isolated ERG6 as a suppressor of a vrp1⌬ growth defect selective for vacuole function. VRP1 encodes verprolin, an actin-binding protein that colocalizes to vacuoles. The vrp1⌬ mutant has fragmented vacuoles in vivo and isolated vacuoles do not fuse in vitro, indicative of a Vrp1p requirement for membrane fusion. ERG6 overexpression rescues vrp1⌬ vacuole fusion in a cytosol-dependent manner. Cytosol prepared from the vrp1⌬ strain remains active; therefore, cytosol is not resupplying Vrp1p. Las17p (Vrp1p functional partner) antibodies, which inhibit wild-type vacuole fusion, do not inhibit the fusion of vacuoles from the vrp1⌬-ERG6 overexpression strain. Vacuole-associated actin turnover is decreased in the vrp1⌬ strain, but recovered by ERG6 overexpression linking sterol enrichment to actin remodeling. Therefore, the Vrp1p/Las17p requirement for membrane fusion is bypassed by increased sterols, which promotes actin remodeling as part the membrane fusion mechanism.

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Molecular species of glycerophospholipids and sphingomyelins of human plasma: Comparison to red blood cells

Cited by 111 publications

References 25 publications

Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins

Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p Requirement

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