Ta Yuan Chang

Summary

Affiliation: Dartmouth Medical School
Country: USA

Publications

  1. ncbi request reprint Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and -2
    T Y Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Curr Opin Lipidol 12:289-96. 2001
  2. ncbi request reprint Niemann-Pick type C disease and intracellular cholesterol trafficking
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 280:20917-20. 2005
  3. doi request reprint Ezetimibe blocks internalization of the NPC1L1/cholesterol complex
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Cell Metab 7:469-71. 2008
  4. pmc Acyl-coenzyme A:cholesterol acyltransferases
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, 1 Rope Ferry Rd, Hanover, NH 03755 1404, USA
    Am J Physiol Endocrinol Metab 297:E1-9. 2009
  5. doi request reprint Neuronal cholesterol esterification by ACAT1 in Alzheimer's disease
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    IUBMB Life 62:261-7. 2010
  6. ncbi request reprint Catalysis of ACAT may be completed within the plane of the membrane: a working hypothesis
    T Y Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755 3844, USA
    J Lipid Res 42:1933-8. 2001
  7. ncbi request reprint Cholesterol sensing, trafficking, and esterification
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Annu Rev Cell Dev Biol 22:129-57. 2006
  8. ncbi request reprint Roles of endogenously synthesized sterols in the endocytic pathway
    Shigeki Sugii
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 281:23191-206. 2006
  9. pmc A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations
    Robert A Maue
    Department of Physiology and Neurobiology, Dartmouth Medical School, Hanover, NH 03755, USA
    Hum Mol Genet 21:730-50. 2012
  10. pmc Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain
    Nobutaka Ohgami
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 101:12473-8. 2004

Research Grants

Collaborators

Detail Information

Publications45

  1. ncbi request reprint Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and -2
    T Y Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Curr Opin Lipidol 12:289-96. 2001
    ..However, further studies at the biochemical and cell biological levels are needed in order to clarify the functional roles of ACAT1 and ACAT2 in the VLDL or chylomicron synthesis/assembly process...
  2. ncbi request reprint Niemann-Pick type C disease and intracellular cholesterol trafficking
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 280:20917-20. 2005
  3. doi request reprint Ezetimibe blocks internalization of the NPC1L1/cholesterol complex
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Cell Metab 7:469-71. 2008
    ..The in vivo significance of these findings is discussed...
  4. pmc Acyl-coenzyme A:cholesterol acyltransferases
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, 1 Rope Ferry Rd, Hanover, NH 03755 1404, USA
    Am J Physiol Endocrinol Metab 297:E1-9. 2009
    ..This chapter summarizes the current knowledge on ACAT-related research in two areas: 1) ACAT genes and proteins and 2) ACAT enzymes as drug targets for atherosclerosis and for Alzheimer's disease...
  5. doi request reprint Neuronal cholesterol esterification by ACAT1 in Alzheimer's disease
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    IUBMB Life 62:261-7. 2010
    ..We also briefly evaluate the potential of ACAT1 as a drug target for AD...
  6. ncbi request reprint Catalysis of ACAT may be completed within the plane of the membrane: a working hypothesis
    T Y Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755 3844, USA
    J Lipid Res 42:1933-8. 2001
    ..MTP then lipidates the growing apolipoprotein B (apoB) chain with CE and TG during the early stages of apoB lipoprotein assembly...
  7. ncbi request reprint Cholesterol sensing, trafficking, and esterification
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Annu Rev Cell Dev Biol 22:129-57. 2006
    ..The nonvesicular cholesterol translocation processes involve the START domain proteins and the oxysterol binding protein-related proteins (ORPs). The properties of these proteins are summarized...
  8. ncbi request reprint Roles of endogenously synthesized sterols in the endocytic pathway
    Shigeki Sugii
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 281:23191-206. 2006
    ..These results also supported the concept that endosomal motility plays an important role in controlling cholesterol trafficking activities...
  9. pmc A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations
    Robert A Maue
    Department of Physiology and Neurobiology, Dartmouth Medical School, Hanover, NH 03755, USA
    Hum Mol Genet 21:730-50. 2012
    ....
  10. pmc Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain
    Nobutaka Ohgami
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 101:12473-8. 2004
    ..Overall, the results demonstrate that there is direct binding between NPC1 and azocholestanol; the binding does not require NPC2 but requires a functional SSD within NPC1...
  11. ncbi request reprint Trafficking defects in endogenously synthesized cholesterol in fibroblasts, macrophages, hepatocytes, and glial cells from Niemann-Pick type C1 mice
    Patrick C Reid
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Lipid Res 44:1010-9. 2003
    ..Our findings suggest that endoCHOL may contribute significantly to the overall cholesterol accumulation observed in selective tissues affected by Niemann-Pick type C disease...
  12. ncbi request reprint Biotinylated theta-toxin derivative as a probe to examine intracellular cholesterol-rich domains in normal and Niemann-Pick type C1 cells
    Shigeki Sugii
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Lipid Res 44:1033-41. 2003
    ..Thus, BCtheta is a powerful tool for visually monitoring cholesterol-rich domains inside normal and NPC cells...
  13. ncbi request reprint Plasma membrane rafts complete cholesterol synthesis by participating in retrograde movement of precursor sterols
    Yoshio Yamauchi
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 282:34994-5004. 2007
    ..Our results reveal a previously undisclosed function of the PM lipid rafts: they bring cholesterol biosynthesis to completion by participating in the retrograde movement of precursor sterols back to the ER...
  14. pmc Purification of recombinant acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) from H293 cells and binding studies between the enzyme and substrates using difference intrinsic fluorescence spectroscopy
    Catherine C Y Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, United States
    Biochemistry 49:9957-63. 2010
    ..These results show that stereospecificity, governed by the 3β-OH moiety in steroid ring A, plays an important role in the binding of cholesterol to ACAT1...
  15. ncbi request reprint A novel cholesterol stain reveals early neuronal cholesterol accumulation in the Niemann-Pick type C1 mouse brain
    Patrick C Reid
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Lipid Res 45:582-91. 2004
    ....
  16. ncbi request reprint The active site His-460 of human acyl-coenzyme A:cholesterol acyltransferase 1 resides in a hitherto undisclosed transmembrane domain
    Zhan Yun Guo
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Biol Chem 280:37814-26. 2005
    ..The results led us to construct a revised, nine-TMD model, with the active site His-460 located within a hitherto undisclosed transmembrane domain, between Arg-443 and Tyr-462...
  17. pmc Investigating the allosterism of acyl-CoA:cholesterol acyltransferase (ACAT) by using various sterols: in vitro and intact cell studies
    Jay Liu
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Biochem J 391:389-97. 2005
    ..Together, our results support the existence of a distinct sterol-activator site in addition to the sterol-substrate site of ACAT1 and demonstrate the applicability of the ACAT1 allosteric model in intact cells...
  18. ncbi request reprint The disulfide linkage and the free sulfhydryl accessibility of acyl-coenzyme A:cholesterol acyltransferase 1 as studied by using mPEG5000-maleimide
    Zhan Yun Guo
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Biochemistry 44:6537-46. 2005
    ..The results show that C92 is located on the cytoplasmic side of the ER membrane and the disulfide is located in the ER lumen, while all other free Cs are located within the hydrophobic region(s) of the enzyme...
  19. ncbi request reprint Synthesis and biochemical properties of a new photoactivatable cholesterol analog 7,7-azocholestanol and its linoleate ester in Chinese hamster ovary cell lines
    Jonathan C Cruz
    Department of Biochemistry, Medical School, Dartmouth College, Hanover, NH, USA
    J Lipid Res 43:1341-7. 2002
    ..These results demonstrate AC as an effective reagent for studying cholesterol-protein interactions involved in intracellular cholesterol trafficking...
  20. ncbi request reprint Distinct endosomal compartments in early trafficking of low density lipoprotein-derived cholesterol
    Shigeki Sugii
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 278:27180-9. 2003
    ..Our results suggest that cholesterol is liberated from LDL cholesteryl ester in the hydrolytic compartment containing AL and then moves to the NPC1-containing late endosome/lysosome before reaching the PM or the endoplasmic reticulum...
  21. ncbi request reprint Mutant acyl-coenzyme A:cholesterol acyltransferase 1 devoid of cysteine residues remains catalytically active
    Xiaohui Lu
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 277:711-8. 2002
    ..Additional studies show that Cys467 is one of the major target sites that leads to p-chloromercuribenzene sulfonic acid-mediated ACAT1 inactivation, suggesting that Cys467 may be near the ACAT active site(s)...
  22. pmc Human acyl-coenzyme A:cholesterol acyltransferase expressed in chinese hamster ovary cells: membrane topology and active site location
    Song Lin
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Mol Biol Cell 14:2447-60. 2003
    ..Instead, a conserved histidine (H434) present within a hydrophobic peptide segment, may be essential for ACAT catalysis. H434 may be located at the cytoplasmic side of the membrane...
  23. ncbi request reprint Role of the N-terminal hydrophilic domain of acyl-coenzyme A:cholesterol acyltransferase 1 on the enzyme's quaternary structure and catalytic efficiency
    Chunjiang Yu
    Biochemistry Department, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Biochemistry 41:3762-9. 2002
    ..2-fold increase in the K(m) for oleoyl-coenzyme. Thus, deleting the dimer-forming motif near the N-terminus changes ACAT1 from its tetrameric form to a dimeric form and increases its catalytic efficiency...
  24. ncbi request reprint Functionality of the seventh and eighth transmembrane domains of acyl-coenzyme A:cholesterol acyltransferase 1
    Zhan Yun Guo
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Biochemistry 46:10063-71. 2007
    ..A similar arrangement is found for residues in TMD8. Thus, helical coils in TMD7 and TMD8 have two distinct functional sides: one side is involved in substrate-binding/catalysis, while the other side is involved in subunit interaction...
  25. ncbi request reprint Cholesterol is superior to 7-ketocholesterol or 7 alpha-hydroxycholesterol as an allosteric activator for acyl-coenzyme A:cholesterol acyltransferase 1
    Yi Zhang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 278:11642-7. 2003
    ..Upon activation by cholesterol, ACAT1 becomes promiscuous toward various sterols as its substrate...
  26. pmc Cellular pregnenolone esterification by acyl-CoA:cholesterol acyltransferase
    Maximillian A Rogers
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 287:17483-92. 2012
    ..Mice lacking LCAT have decreased levels of PREG esters in the adrenals. These results suggest LCAT along with ACAT1/ACAT2 contribute to control pregnenolone ester content in different cell types and tissues...
  27. ncbi request reprint Human acyl-CoA:cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis
    Catherine Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Acta Biochim Biophys Sin (Shanghai) 38:151-6. 2006
    ..This review briefly outlines the current knowledge on the biochemical properties of human ACATs, and then focuses on discussing the merit of ACAT as a drug target for pharmaceutical interventions against atherosclerosis...
  28. pmc Transport of LDL-derived cholesterol from the NPC1 compartment to the ER involves the trans-Golgi network and the SNARE protein complex
    Yasuomi Urano
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 105:16513-8. 2008
    ..These results show that vesicular trafficking is involved in transporting a significant portion of LDL-CHOL from the NPC1-containing endosomal compartment to the TGN before its arrival at the ER...
  29. pmc Acyl-coenzyme A:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer's disease mouse and reduces human P301L-tau content at the presymptomatic stage
    Yohei Shibuya
    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
    Neurobiol Aging 36:2248-59. 2015
    ..These results suggest that, in addition to ameliorating amyloidopathy in both young and old AD mice, ACAT1 blockage may benefit AD by reducing tauopathy at early stage...
  30. pmc Inhibiting ACAT1/SOAT1 in microglia stimulates autophagy-mediated lysosomal proteolysis and increases Aβ1-42 clearance
    Yohei Shibuya
    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755
    J Neurosci 34:14484-501. 2014
    ..Autophagy is needed to degrade misfolded proteins/peptides. Our results implicate that blocking ACAT1 may provide a new way to benefit multiple neurodegenerative diseases. ..
  31. pmc Acyl-coenzyme A:cholesterol acyltransferase 1 - significance of single-nucleotide polymorphism at residue 526 and the role of Pro347 near the fifth transmembrane domain
    Li Hao Huang
    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
    FEBS J 281:1773-83. 2014
    ..Overall, our results imply that the CAG/CGG polymorphism can be utilized to perform ACAT1 activity/human disease susceptibility studies, and that Pro347 located near TMD5 plays an important role in modulating enzyme catalysis...
  32. pmc Partial blockage of sterol biosynthesis with a squalene synthase inhibitor in early postnatal Niemann-Pick type C npcnih null mice brains reduces neuronal cholesterol accumulation, abrogates astrogliosis, but may inhibit myelin maturation
    Patrick C Reid
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Neurosci Methods 168:15-25. 2008
    ..The methods described in the current work have general applicability for lipid metabolism studies in mice brains in various pathophysiological conditions...
  33. pmc ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD
    Elena Y Bryleva
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 107:3081-6. 2010
    ..Our study supports the potential of ACAT1 as a therapeutic target for treating certain forms of AD...
  34. doi request reprint Acyl-CoA:cholesterol acyltransferases (ACATs/SOATs): Enzymes with multiple sterols as substrates and as activators
    Maximillian A Rogers
    Department of Biochemistry, Geisel School of Medicine, Dartmouth HB7200, Hanover, NH 03755, United States Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, United States
    J Steroid Biochem Mol Biol 151:102-7. 2015
    ..This article is part of a Special Issue entitled 'Steroid/Sterol signaling'. ..
  35. pmc Acat1 knockdown gene therapy decreases amyloid-β in a mouse model of Alzheimer's disease
    Stephanie R Murphy
    The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
    Mol Ther 21:1497-506. 2013
    ..This study provides support for the potential therapeutic use of Acat1 knockdown gene therapy in AD. ..
  36. pmc Acat1 gene ablation in mice increases hematopoietic progenitor cell proliferation in bone marrow and causes leukocytosis
    Li Hao Huang
    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
    Arterioscler Thromb Vasc Biol 33:2081-7. 2013
    ..To investigate the role of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) in hematopoiesis...
  37. ncbi request reprint Acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) is induced in monocyte-derived macrophages: in vivo and in vitro studies
    Naomi Sakashita
    Second Department of Pathology, Kumamoto University School of Medicine, Kumamoto, Japan
    Lab Invest 83:1569-81. 2003
    ..We conclude that under various pathologic conditions, fully differentiated macrophages express ACAT2 in addition to ACAT1...
  38. ncbi request reprint Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism
    Nadeem Khan
    Department of Diagnostic Radiology, EPR Center, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Biochemistry 42:23-9. 2003
    ..The results indicate that the concentration of cholesterol in the plasma membrane can be an important factor for the magnitude of the oxygen gradient observed across the cell membrane...
  39. ncbi request reprint Human acyl-coenzyme A:cholesterol acyltransferase 1 (acat1) sequences located in two different chromosomes (7 and 1) are required to produce a novel ACAT1 isoenzyme with additional sequence at the N terminus
    Li Yang
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Rd, Shanghai 200031, China
    J Biol Chem 279:46253-62. 2004
    ..To our knowledge, our result provides the first mammalian example that a trans-spliced mRNA produces a functional protein...
  40. ncbi request reprint Transport of plasma membrane-derived cholesterol and the function of Niemann-Pick C1 Protein
    Volker Wiegand
    Institute of Biochemistry, Johannes Gutenberg University of Mainz, Germany
    FASEB J 17:782-4. 2003
    ..Our data show that NPC1 has an essential role in the distribution of plasma membrane-derived cholesterol by maintaining the small size of cholesterol-containing lipid droplets in the cell...
  41. ncbi request reprint Intracellular cholesterol mobilization involved in the ABCA1/apolipoprotein-mediated assembly of high density lipoprotein in fibroblasts
    Yoshio Yamauchi
    Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho cho, Mizuho ku, Nagoya 467 8601, Japan
    J Lipid Res 45:1943-51. 2004
    ..The cholesterol mobilization process is presumably related to PKC activation by apoA-I...
  42. ncbi request reprint Promotion of tau phosphorylation by MAP kinase Erk1/2 is accompanied by reduced cholesterol level in detergent-insoluble membrane fraction in Niemann-Pick C1-deficient cells
    Naoya Sawamura
    Department of Dementia Research, National Institute for Longevity Sciences, 36 3 Gengo, Morioka, Obu, Aichi 474 8522, Japan
    J Neurochem 84:1086-96. 2003
    ....
  43. pmc Human acyl-CoA:cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma
    Bao Liang Song
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Biochem J 394:617-26. 2006
    ..Thus, the elevated ACAT2 expression may serve as a new biomarker for certain form(s) of hepatocellular carcinoma...
  44. ncbi request reprint A stable upstream stem-loop structure enhances selection of the first 5'-ORF-AUG as a main start codon for translation initiation of human ACAT1 mRNA
    Li Yang
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences
    Acta Biochim Biophys Sin (Shanghai) 36:259-68. 2004
    ..This work showed that a stable upstream stem-loop structure could modulate the start codon selection during translation initiation of mRNAs that contain adjacent multi-5'-ORF-AUGs...
  45. ncbi request reprint Two human ACAT2 mRNA variants produced by alternative splicing and coding for novel isoenzymes
    Xiao Min Yao
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Acta Biochim Biophys Sin (Shanghai) 37:797-806. 2005
    ..Our findings might help to understand the regulation of the ACAT2 gene expression under certain physiological and pathological conditions...

Research Grants1

  1. Attenuating sterol synthesis in WT and NPC mice brains
    Ta Yuan Chang; Fiscal Year: 2005
    ..Specific Aim 3: To examine the long-term effect of SSI CP-340868 at 2 different doses on life spans of normal and NPC1 mice. ..