Intracellular Cholesterol Trafficking
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Intracellular Cholesterol Trafficking
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Author : T.Y. Chang
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Intracellular Cholesterol Trafficking written by T.Y. Chang and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Science categories.
INTRODUCTION AND RATIONALE FOR INTRACELLULAR CHOLESTEROL TRAFFICKING This volume is an elaboration of an earlier small meeting held in St. Louis, Missouri. In April 1997, many of the authors met for a two-day meeting devoted entirely to intracellular cholesterol trafficking. The rationale for this meeting was that investigators interested in this topic worked in a variety of fields, and rarely, if ever, all met together. Everybody knew each other's papers but mostly worked in isolation from one another. Understanding of cholesterol trafficking also appeared to have reached the point where it would start to rapidly expand beyond these few laboratories. Understanding of cholesterol trafficking was moving from a largely descriptive science into the molecular age. It seemed a good time to get together and see how much we agreed upon up to this point. More authors contributed to this volume than attended the St. Louis meeting. That meeting was generously funded by grants from Bristol-Myers Squibb, Merck and Company and Parke-Davis, however, the total funding available limited the size of the meeting. For the book, we are not so limited and have tried to be as inclusive as possible and pretty much invited everyone who is presently active in this area. We were quite fortunate to successfully recruit the authors we sought for each of these chapters. The authors and their contributions can be organized by particular interests and particular areas of expertise.
Intracellular Cholesterol Trafficking In Cho Cells Defective In Npc1
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Author : Jonathan C. Cruz
language : en
Publisher:
Release Date : 2000
Intracellular Cholesterol Trafficking In Cho Cells Defective In Npc1 written by Jonathan C. Cruz and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with Cholesterol categories.
The Box C D Snorna U60 Regulates Intracellular Cholesterol Trafficking
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Author : Katrina Adelle Brandis
language : en
Publisher:
Release Date : 2013
The Box C D Snorna U60 Regulates Intracellular Cholesterol Trafficking written by Katrina Adelle Brandis and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with Electronic dissertations categories.
Mobilization of plasma membrane (PM) cholesterol to the endoplasmic reticulum (ER) is essential for cellular cholesterol homeostasis. The mechanisms regulating this retrograde, intermembrane cholesterol transfer are not well understood. Since mutant cells with defects in PM to ER cholesterol trafficking can be isolated on the basis of resistance to amphotericin B, we conducted an amphotericin B loss-of-function screen in Chinese hamster ovary (CHO) cells using insertional mutagenesis to identify genes that regulate this trafficking mechanism. Mutant line A1 displayed reduced cholesteryl ester formation from PM-derived cholesterol and increased de novo cholesterol synthesis, indicating a deficiency in retrograde cholesterol transport. Genotypic analysis revealed that the A1 cell line contained one disrupted allele of the U60 snoRNA host gene, resulting in haploinsufficiency of the box C/D snoRNA U60. Complementation and mutational studies revealed the U60 snoRNA to be the essential feature from this locus that affects cholesterol trafficking. Lack of alteration in predicted U60-mediated site-directed methylation of 28S rRNA in the A1 mutant suggests that the U60 snoRNA modulates cholesterol trafficking by a mechanism that is independent of this canonical function. Additional studies were conducted to isolate and identify direct RNA targets of the U60 snoRNA and to define cellular pathways that are affected by U60 expression. This study adds to a growing body of evidence for participation of small non-coding RNAs in cholesterol homeostasis and is the first to implicate a snoRNA in this cellular function.
Tmem97 Regulates Intracellular Cholesterol Trafficking By Controlling Npc1 Protein Levels
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Author : Fabian Bartz
language : en
Publisher:
Release Date : 2011
Tmem97 Regulates Intracellular Cholesterol Trafficking By Controlling Npc1 Protein Levels written by Fabian Bartz and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
Npc1 Mediated Trafficking Of Intracellular Cholesterol
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Author : Shigeki Sugii
language : en
Publisher:
Release Date : 2003
Npc1 Mediated Trafficking Of Intracellular Cholesterol written by Shigeki Sugii and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with Cholesterol categories.
Cholesterol Transporters Of The Start Domain Protein Family In Health And Disease
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Author : Barbara J. Clark
language : en
Publisher: Springer
Release Date : 2014-07-24
Cholesterol Transporters Of The Start Domain Protein Family In Health And Disease written by Barbara J. Clark and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-24 with Medical categories.
Non-vesicular intracellular cholesterol transport is an important mechanism for maintaining membrane cholesterol homeostasis. Recent reports of studies directed at soluble cholesterol transport proteins indicate that aberrant expression of the START proteins may contribute to disease states associated with disorders in cholesterol homeostasis. This is an exciting new direction in the field and the purpose of this book will be to highlight the current research directed at potential roles for the START family in diabetes, cancer and atherogenesis. This book also provides a personal and historical perspective of the discovery-to-publication journey that the authors had for their particular START domain family member. The goal will be to provide perspectives to graduate students, post-doctoral fellows and endocrinology fellows on the research discovery process.
Characterization Of The Nogo B Receptor
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Author : Kenneth Douglas Harrison
language : en
Publisher:
Release Date : 2009
Characterization Of The Nogo B Receptor written by Kenneth Douglas Harrison and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009 with categories.
Snorna U17 As A Novel Regulator Of Cholesterol Homeostasis
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Author : Sarah Jinn
language : en
Publisher:
Release Date : 2014
Snorna U17 As A Novel Regulator Of Cholesterol Homeostasis written by Sarah Jinn and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with Electronic dissertations categories.
Cholesterol is an essential cellular lipid that is a regulator of membrane organization and fluidity, and is an obligate precursor for synthesis of steroid hormones, oxysterols and bile acids. Cellular cholesterol homeostasis is tightly regulated through a network of transcriptional and non-transcriptional pathways. To further delineate intracellular cholesterol trafficking pathways, we initiated a loss-of-function genetic screen in Chinese hamster ovary cells (CHO), selecting for CHO mutants with altered cholesterol trafficking. Here we characterize one of the isolated mutants in which the locus encoding small nucleolar RNA hosting gene 3 (SNHG3) is disrupted. Altered cholesterol trafficking phenotype is not due to reduced expression of the SNHG3 mRNA, but rather results from haploinsufficiency of the H/ACA small nucleolar RNA (snoRNA) U17, a small non-coding RNA produced from the hosting gene SNHG3 introns. Previously identified function of U17 snoRNA is to mediate 18S rRNA processing, yet cells haploinsufficient for U17 show normal maturation and amount of 18S rRNA, indicating that altered cholesterol trafficking is not caused by defects in rRNA processing. Through expression profiling, we identify that mRNA of mitochondrial adapter protein HUMMR is a target that is negatively regulated by U17 snoRNA. HUMMR mRNA is up-regulated U17 snoRNA-deficient cells and down-regulated in U17 snoRNA-overexpression cells. Up-regulation of HUMMR itself is sufficient to alter cholesterol trafficking, suggesting HUMMR functions downstream of U17 snoRNA-initiated regulation of cholesterol homeostasis. We show that up-regulation of HUMMR protein in U17 snoRNA-deficient cells promotes formation of ER-mitochondrial contacts, decreasing esterification of cholesterol and facilitating cholesterol trafficking to mitochondria, which increases the synthesis of 27-hydroxy cholesterol and pregnenolone in mitochondria. We also show that levels of U17 snoRNA and HUMMR are developmentally regulated in steroidogenic tissues. As HUMMR level increases in maturing ovarian tissue, expression of U17 snoRNA gradually decreases. This suggests negative regulation of HUMMR by U17 snoRNA in vivo that may be critical for regulation of steroidogenesis. Together, this dissertation describes U17 snoRNA as a new class of non-coding RNA that modulates cholesterol trafficking by regulating downstream coding genes. U17 snoRNA and HUMMR regulate mitochondrial synthesis of steroids, and are developmentally regulated in steroidogenic tissues, suggesting that the U17 snoRNA-HUMMR pathway may serve a previously unrecognized, physiological role in gonadal tissue maturation and steroidogenesis.
Role Of The Niemann Pick Type C1 Protein In Trafficking And Homeostasis Of Intracellular Cholesterol
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Author : Elizabeth Erin Millard
language : en
Publisher:
Release Date : 2003
Role Of The Niemann Pick Type C1 Protein In Trafficking And Homeostasis Of Intracellular Cholesterol written by Elizabeth Erin Millard and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.
Studies On The Mechanisms Of Mitochondrial Cholesterol Transport And Steroidogenesis
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Author : Amy Hengyi Zhao
language : en
Publisher:
Release Date : 2019
Studies On The Mechanisms Of Mitochondrial Cholesterol Transport And Steroidogenesis written by Amy Hengyi Zhao and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
Cholesterol is among one of the most decorated molecules in biology today, the study of which produced not only a number of Nobel Prizes but also key findings that influence our study of physiology and medicine today. It is the single starting substrate of the steroidogenic pathway, the synthesis of steroid hormones such as progesterone, testosterone, and corticosterone, which control a variety of essential physiological and metabolic functions including salt and water balance, spermatogenesis, follicular development and maintenance of pregnancy. Steroidogenesis is a unique process in which all of the steroid hormones are derived from a single substrate, cholesterol, by the CYP11A1 enzyme located on the matrix side of the inner mitochondrial membrane. Steroidogenesis is rapidly triggered in response to induction by tropic hormones such as ACTH or LH binding to their respective G-protein coupled receptors on the plasma membrane, triggering a rise in intracellular cAMP. This process, however, requires that cholesterol be trafficked across the aqueous intermembrane space, a substantial obstacle for the steroidogenic cell due to cholesterol's extreme hydrophobicity. My studies provide evidence that this intramitochondrial trafficking is facilitated by the steroidogenic acute regulatory protein (STAR) and not the translocator protein (TSPO). My studies conclusively eliminate TSPO from our current models of the steroidogenic process and demonstrate that a TSPO ligand that has been shown to reduce progesterone synthesis is, in fact, an inhibitor of 3b-HSD, a downstream enzyme of progesterone synthesis. During my studies, I also generated STAR knockout MA-10 Leydig cell lines, the first in vitro model of STAR deletion in a steroidogenic cell line, providing evidence that induction of STAR expression is required for the steroidogenic process and that this role cannot be compensated for by TSPO. My studies also demonstrate that extracellular cholesterol sources, such as serum lipoproteins, can contribute to the total pool of cholesterol substrate utilized by the cell to synthesize steroid hormones. I also characterize a group of hCG-responsive MA-10 cells, an improved model system for the ongoing study of steroidogenic pathways beyond the mitochondria. I also provide evidence that changes in ER cholesterol synthesis in MA-10 cells can influence expression of the STAR protein, pointing toward the possible involvement of the sterol regulatory element binding protein (SREBP) family of transcription factors. These studies set the stage for the study of cholesterol trafficking pathways beyond the mitochondria and characterize models that can be used as a tool to study cholesterol sourcing and trafficking proteins that support steroidogenesis.