Altered sensitivities to potential inhibitors of cholesterol biosynthesis in Niemann-Pick type C fibroblasts.

Abstract:

:Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are characterized by the lysosomal accumulation of unesterified cholesterol and the inability of low-density lipoprotein (LDL) to stimulate cholesterol esterification, in addition to impaired LDL-mediated down-regulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in the transport of cholesterol from lysosomes to other intracellular membrane sites has been suggested, it is unclear how cells regulate the levels of cellular sterols and whether their membrane cholesterol requirements are satisfied or not. We studied the esterification of exogenously added cholesterol, total levels of cellular cholesterol and cholesteryl ester, cholesterol synthesis from a two-carbon precursor, and sensitivities to potential inhibitors of cholesterol biosynthesis in proliferating NP-C cells. We observed the following: (a) esterification of [3H]cholesterol was decreased but the total amount of cellular cholesteryl ester was not decreased; (b) synthesis of cholesterol from [3H]acetate was increased; and (c) cells were hypersensitive to cholecalciferol, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, and were resistant to filipin, which binds to membrane sterols and presumably damages the membrane. The results indicate that NP-C cells depend on the cellular cholesterol synthetic pathway for their proliferation, but the plasma membrane sterols are presumably decreased. The altered sensitivities to potential inhibitors of cholesterol biosynthesis should be a useful marker for diagnosis and genetic studies.

journal_name

Cell Struct Funct

authors

Ohno K,Nanba E,Nakano T,Inui K,Okada S,Takeshita K

doi

10.1247/csf.18.231

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

231-40

issue

4

eissn

0386-7196

issn

1347-3700

journal_volume

18

pub_type

杂志文章
  • Inhibitory effect of dideoxyforskolin on cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin in MDCK cells.

    abstract::We have found that 1,9-Dideoxyforskolin (DDF) strongly inhibited the cell death induced by ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in MDCK cells, suggesting that these protein toxins have a DDF-sensitive common pathway leading to cell death. However, no significant effect of forskolin on these toxins ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.22.545

    authors: Oda T,Komatsu N,Muramatsu T

    更新日期:1997-10-01 00:00:00

  • Developmental changes of synapsin I subcellular localization in rat cerebellar neurons.

    abstract::Synapsin I, one of the major synaptic proteins, is thought to associate with synaptic vesicles and to play a regulatory role in neurotransmitter release. In mature neurons, it is concentrated almost exclusively in presynaptic nerve endings. Here, we studied the subcellular localization of synapsin I during the develop...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.15.329

    authors: Harada A,Sobue K,Hirokawa N

    更新日期:1990-12-01 00:00:00

  • Population-dependent requirements of vitamin B12 and metabolically related substances of several mouse cell types in serum-free, albumin-fortified medium.

    abstract::Mouse FM3A cells propagated well in serum-free medium containing 0.5% serum albumin and 1 microgram of insulin/ml. The vitamin B12 (B12) requirement of the cells depended on the population density. This requirement disappeared when a sufficiently large cell population was present. A combination of 1-100 ng of B12/ml a...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.11.9

    authors: Matsuya Y,Yamane I

    更新日期:1986-03-01 00:00:00

  • Novel insights into Chk1 regulation by phosphorylation.

    abstract::Checkpoint kinase 1 (Chk1) is a conserved protein kinase central to the cell-cycle checkpoint during DNA damage response (DDR). Until recently, ATR, a protein kinase activated in response to DNA damage or stalled replication, has been considered as the sole regulator of Chk1. Recent progress, however, has led to the i...

    journal_title:Cell structure and function

    pub_type: 杂志文章,评审

    doi:10.1247/csf.14017

    authors: Goto H,Kasahara K,Inagaki M

    更新日期:2015-01-01 00:00:00

  • Tenascin-C splice variant adhesive/anti-adhesive effects on chondrosarcoma cell attachment to fibronectin.

    abstract::Tenascin-C is an oligomeric glycoprotein of the extracellular matrix that has been found to have both adhesive and anti-adhesive properties for cells. Recent elucidation of the two major TNC splice variants (320 kDa and 220 kDa) has shed light on the possibility of varying functions of the molecule based on its splici...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.26.179

    authors: Ghert MA,Qi WN,Erickson HP,Block JA,Scully SP

    更新日期:2001-06-01 00:00:00

  • Total internal reflection fluorescence microscopy for single-molecule imaging in living cells.

    abstract::Marvelous background rejection in total internal reflection fluorescence microscopy (TIR-FM) has made it possible to visualize single-fluorophores in living cells. Cell signaling proteins including peptide hormones, membrane receptors, small G proteins, cytoplasmic kinases as well as small signaling compounds have bee...

    journal_title:Cell structure and function

    pub_type: 杂志文章,评审

    doi:10.1247/csf.27.357

    authors: Sako Y,Uyemura T

    更新日期:2002-10-01 00:00:00

  • The relation between length of the cell cycle duration and RNA content in HeLa S3 cells.

    abstract::The cell cycle of HeLa S3 cells synchronized by hydroxyurea was investigated by flow cytometry. Metachromatic fluorochrome acridine orange was used to strain the DNA and RNA of the cells differentially. Periodic changes in the cellular DNA and RNA contents were observed through five cell cycles. The G1 and S phases of...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.8.303

    authors: Fujikawa-Yamamoto K

    更新日期:1983-09-01 00:00:00

  • Selective expression of mutated p53 in human cells immortalized with either 4-nitroquinoline 1-oxide or 60Co gamma rays.

    abstract::Many studies on in vitro transformation of human cells indicate that the cells must be immortalized before they can be neoplastically transformed, indicating that immortalization is a critical step in multistep neoplastic transformation of human cells. We immortalized three human cell lines by repeated treatment with ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.21.111

    authors: Mihara K,Iijima M,Kondo T,Namba M

    更新日期:1996-04-01 00:00:00

  • Novel actin rods appeared in spores of Dictyostelium discoideum.

    abstract::When spores of Dictyostelium discoideum matured through normal development were stained with rhodamine-phalloidin, rod-shaped fluorescence was found across the nucleus and in the cytoplasm. Electron micrographs of the rod shape showed that it consisted of long and straight fibers 12 nm in diameter. In contrast, a conv...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.19.189

    authors: Sameshima M,Chijiiwa Y,Kishi Y,Hashimoto Y

    更新日期:1994-08-01 00:00:00

  • Microtuble organization in Xenopus eggs during the first cleavage and its role in cytokinesis.

    abstract::It has been suggested that the organization of microtubules during mitosis plays an important role in cytokinesis in animal cells. We studied the organization of microtubules during the first cleavage and its role in cytokinesis of Xenopus eggs. First, we examined the immunofluorescent localization of microtubules in ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.27.163

    authors: Takayama M,Noguchi T,Yamashiro S,Mabuchi I

    更新日期:2002-08-01 00:00:00

  • c-myc induces autophagy in rat 3Y1 fibroblast cells.

    abstract::The proto-oncogene c-myc is a multifunctional gene that regulates cell division, cell growth, and apoptosis. Here we report a new function of c-myc: induction of autophagy. Autophagy is a bulk degradation system for intracellular proteins. Autophagy proceeds with characteristic morphologies, which begins with the form...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.28.195

    authors: Tsuneoka M,Umata T,Kimura H,Koda Y,Nakajima M,Kosai K,Takahashi T,Takahashi Y,Yamamoto A

    更新日期:2003-06-01 00:00:00

  • Establishment and characterization of tracheal epithelial cell lines, TM01 and TM02-3, from transgenic mice bearing temperature-sensitive simian virus 40 large T-antigen gene.

    abstract::Murine tracheal epithelial cell lines, TM01 and TM02-3, were established from a primary culture of tracheal cells of adult transgenic mice bearing a temperature-sensitive simian virus (SV40) large T-antigen gene. Both TM01 and TM02-3 cells, which grew until confluent monolayers were formed, maintained tight contact wi...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.23.119

    authors: Sugiyama N,Tabuchi Y,Numata F,Uchida Y,Horiuchi T,Ishibashi K,Ono S,Obinata M,Furusawa M

    更新日期:1998-06-01 00:00:00

  • Neuronal differentiation of mouse neural crest cells in vitro.

    abstract::The purpose of the present study is to analyze the effect of serum or chick embryo extract (CEE) on the neuronal differentiation of the mouse neural crest cells. When the crest cells were cultured in the medium containing serum at low concentration (5% calf serum), neurite outgrowth was observed. The active outgrowth ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.13.267

    authors: Ito K,Morita T,Takeuchi T

    更新日期:1988-06-01 00:00:00

  • High voltage electric pulses efficiently induce fusion of cells in monolayer culture.

    abstract::High voltage electric pulses, 1000 V/cm, were found to induce cell fusion efficiently when delivered to cells growing in a monolayer culture. The maximum yield of fused cells was about 30% of cells remaining after treatment. Colonies of interspecies hybrid cells between mouse and others also appeared with a frequency ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.14.173

    authors: Ishizaki K,Chang HR,Eguchi T,Ikenaga M

    更新日期:1989-04-01 00:00:00

  • Luminal domain of ATF6 alone is sufficient for sensing endoplasmic reticulum stress and subsequent transport to the Golgi apparatus.

    abstract::The transcription factor ATF6 is constitutively synthesized as a type II transmembrane protein embedded in the endoplasmic reticulum (ER). When unfolded proteins accumulate in the ER, ATF6 senses such ER stress via an as yet undetermined mechanism and relocates to the Golgi apparatus where it is cleaved by sequential ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.10010

    authors: Sato Y,Nadanaka S,Okada T,Okawa K,Mori K

    更新日期:2011-01-01 00:00:00

  • Immunocytochemical analysis of peptide hormone processing: importance of the positively charged N-terminal domain of signal peptide in correct ER targeting in yeast cells.

    abstract::We used a morphological approach to determine the topogenic role of the signal peptide in mediating the ER translocation of yeast prepro-alpha-factor. In prepro-alpha-factor-somatostatin hybrids, changes in the N-terminal amino acid sequence from wild-type NH2-Met-Arg-Phe (MRF) to NH2-Met-Phe-Lys (MFK) caused a subtle...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.22.365

    authors: Cheong KH,Park SD,Kim J,Hong SH

    更新日期:1997-06-01 00:00:00

  • Inhibition of nuclear envelope reconstitution in Xenopus interphase egg extract by hemin.

    abstract::Addition of hemin to the nuclear reconstitution system of Xenopus interphase egg extract using sperm head chromatin resulted in abnormal pseudonuclei exhibiting flattened membrane patches randomly distributed both on the surface and inside the nuclei. The structures that resembled nuclear pores were observed on these ...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.23.291

    authors: Nishiyama R,Ikami M,Yamao F,Tsuchida S,Yagura T

    更新日期:1998-10-01 00:00:00

  • Different effects of all-trans-retinoic acid on phorbol ester-stimulated and phytohemagglutinin-stimulated interleukin-2 expression in human T-cell lymphoma HUT-78 cells.

    abstract::In view of the importance of vitamin A in the human immune system and the central role of interleukin-2 (IL-2) in the proliferation of T-lymphocytes, we examined the effects of all-trans-retinoic acid (ATRA) on the protein and gene expression of IL-2 in the human T-cell line HUT-78 when stimulated with either 12-O-tet...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.07020

    authors: Goto S,Okada N,Kaneko A,Isemura M

    更新日期:2008-01-01 00:00:00

  • Flagellar-associated Protein FAP85 Is a Microtubule Inner Protein That Stabilizes Microtubules.

    abstract::Genomics and proteomics studies in Chlamydomonas have revealed that an axoneme is composed of 200-600 types of proteins, including uncharacterized proteins collectively named flagellar-associated proteins (FAPs). Nine FAPs contain the EF-hand motif; however, they have not yet been well characterized. To find component...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.17023

    authors: Kirima J,Oiwa K

    更新日期:2018-02-16 00:00:00

  • Further characterization of the cation channel of a yeast vacuolar membrane in a planar lipid bilayer.

    abstract::A voltage-dependent and Ca2(+)-activated cation channel recently found in the vacuolar membrane of the yeast Saccharomyces cerevisiae was incorporated into planar lipid bilayers and further characterized in macroscopic and single channel levels. Single channel conductances for various cations were in the order: NH4+ g...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.14.659

    authors: Sato M,Tanifuji M,Kasai M

    更新日期:1989-12-01 00:00:00

  • Hemocytes release phenoloxidase upon contact reaction, an allogeneic interaction, in the ascidian Halocynthia roretzi.

    abstract::Contact reaction is the morphological expression of allogeneic recognition by hemocytes in the ascidian, Halocynthia roretzi; namely they undergo an exocytotic burst upon contact with non-self (allogeneic) hemocytes in vitro. We have found that contact reaction is accompanied by a burst of cyanide-insensitive oxygen c...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.20.81

    authors: Akita N,Hoshi M

    更新日期:1995-02-01 00:00:00

  • Intracellular localization and partial amino acid sequence of a stress-inducible 40-kDa protein in HeLa cells.

    abstract::We earlier discovered a novel 40-kDa protein (hsp40) induced by heat shock and other stresses in mammalian and avian cells. In this report, we purified the hsp40 in HeLa cells, using modified two-dimensional gel electrophoresis, and determined the amino terminal amino acid sequence of this protein. The hsp40 is homolo...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.17.77

    authors: Hattori H,Liu YC,Tohnai I,Ueda M,Kaneda T,Kobayashi T,Tanabe K,Ohtsuka K

    更新日期:1992-02-01 00:00:00

  • Angiogenic activity of a fusion protein of the cell-binding domain of fibronectin and basic fibroblast growth factor.

    abstract::We constructed a fusion protein of the cell-binding domain of human fibronectin and human basic fibroblast growth factor, and prepared a polypeptide with both cell-adhesive activity and growth factor activity. A human gene fragment coding for basic fibroblast growth factor was amplified by the polymerase chain reactio...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.19.37

    authors: Hashi H,Hatai M,Kimizuka F,Kato I,Yaoi Y

    更新日期:1994-02-01 00:00:00

  • Regional variation and function of nucleotide and amino acid sequence.

    abstract::Two methods of qualitative analysis of sequence distribution in DNA and protein are presented. The first method is based on the finding that the frequency of occurrence of each nucleotide in a defined sequence with functional significance more or less deviates from uniform distribution. The deviation found in this def...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.13.387

    authors: Kiho Y

    更新日期:1988-10-01 00:00:00

  • The molecular mechanism of targeted vesicle transport in cytokinesis.

    abstract::Recent studies have demonstrated that vesicle transport to cleavage furrow is indispensable for cytokinesis. Some animal and plant cells form distinct structures during cell division known as central spindle and phragmoplast, respectively. Several essential factors involved in the vesicle transport have been isolated ...

    journal_title:Cell structure and function

    pub_type: 杂志文章,评审

    doi:10.1247/csf.26.567

    authors: Edamatsu M

    更新日期:2001-12-01 00:00:00

  • Hepatic stellate cells: unique characteristics in cell biology and phenotype.

    abstract::Hepatic stellate cells (HSCs), a mesenchymal cell type in hepatic parenchyma, have unique features with respect to their cellular origin, morphology, and function. Normal, quiescent HSCs function as major vitamin A-storing cells containing over 80% of total vitamin A in the body to maintain vitamin A homeostasis. HSCs...

    journal_title:Cell structure and function

    pub_type: 杂志文章,评审

    doi:10.1247/csf.28.105

    authors: Sato M,Suzuki S,Senoo H

    更新日期:2003-04-01 00:00:00

  • Bypass of the ts block of tsJT60, a G0-specific ts mutant from rat fibroblasts, by fetal bovine serum and epidermal growth factor.

    abstract::tsJT60, a temperature-sensitive (ts) G0-mutant cell line from a Fischer rat, grows normally in the exponential growth phase at 34 degrees C and 39.5 degrees C, but when stimulated with fetal bovine serum (FBS), from the G0 phase they reenter the S phase at 34 degrees C but not at 39.5 degrees C. The ts-block was bypas...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.12.421

    authors: Ninomiya-Tsuji J,Nakahara Y,Ito C,Akiyama T,Ishibashi S,Ide T

    更新日期:1987-10-01 00:00:00

  • Soluble sperm extract triggers inositol 1,4,5-trisphosphate-induced Ca2+ release in the oocytes of the sea urchin, Anthocidaris crassispina.

    abstract::The substance in sperm which induces the activation of eggs at fertilization has yet to be elucidated. Osawa et al. reported that the soluble extract of sperm (spex) causes inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) in fertilized eggs of sea urchins when externally applied [Osawa et al., (1992). Zo...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.19.73

    authors: Osawa M

    更新日期:1994-04-01 00:00:00

  • Overexpression of PRA2, a Rab/Ypt-family small GTPase from Pea Pisum sativum, aggravates the growth defect of yeast ypt mutants.

    abstract::A large number of Rab/Ypt-family small GTPases have been identified from higher plants. While some of them can complement yeast ypt mutants, the expression of Arabidopsis Ara4 protein aggravated the growth defect of a subset of ypt mutants, probably because of the titration of common regulator(s) of yeast Ypt proteins...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.25.11

    authors: Matsuda N,Ueda T,Sasaki Y,Nakano A

    更新日期:2000-02-01 00:00:00

  • Inhibition of cell proliferation by a unique lysophosphatidic acid, PHYLPA, isolated from Physarum polycephalum: signaling events of antiproliferative action by PHYLPA.

    abstract::The unique Physarum lysophosphatidic acid, PHYLPA, having a cyclopropane in the fatty acid moiety and a cyclic phosphate at C-2 and C-3 positions of the glycerol, inhibited proliferation of human fibroblast cells, TIG-3 and TIG-7, which were cultured in a chemically defined (serum-free) medium. The cells at S- and M-p...

    journal_title:Cell structure and function

    pub_type: 杂志文章

    doi:10.1247/csf.18.363

    authors: Murakami-Murofushi K,Kaji K,Kano K,Fukuda M,Shioda M,Murofushi H

    更新日期:1993-10-01 00:00:00