Abstract:
:Low-density lipoprotein (LDL) deposition, aggregation and retention in the endothelial sub-intima are critical initiating events during atherosclerosis. Macrophages digest aggregated LDL (agLDL) through a process called exophagy. High-density lipoprotein (HDL) plays an atheroprotective role, but studies attempting to exploit it therapeutically have been unsuccessful, highlighting gaps in our current understanding of HDL function. Here, we characterized the role of HDL during exophagy of agLDL. We find that atherosclerotic plaque macrophages contact agLDL and form an extracellular digestive compartment similar to that observed in vitro During macrophage catabolism of agLDL in vitro, levels of free cholesterol in the agLDL are increased. HDL can extract free cholesterol directly from this agLDL and inhibit macrophage foam cell formation. Cholesterol-balanced hydroxypropyl-β-cyclodextrin similarly reduced macrophage cholesterol uptake and foam cell formation. Finally, we show that HDL can directly extract free cholesterol, but not cholesterol esters, from agLDL in the absence of cells. Together, these results suggest that the actions of HDL can directly extract free cholesterol from agLDL during catabolism, and provide a new context in which to view the complex relationship between HDL and atherosclerosis.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Singh RK,Lund FW,Haka AS,Maxfield FRdoi
10.1242/jcs.237271subject
Has Abstractpub_date
2019-12-02 00:00:00issue
23eissn
0021-9533issn
1477-9137pii
jcs.237271journal_volume
132pub_type
杂志文章abstract::Transforming growth factor beta (TGFbeta) plays an important role in development and maintenance of murine yolk sac vascular development. Targeted deletions of Tgfb1 and other components of this signaling pathway, such as Acvrl1, Tgfbr1 and Tgfbr2, result in abnormal vascular development especially of the yolk sac, le...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02788
更新日期:2006-02-15 00:00:00
abstract::Receptor protein tyrosine phosphatase beta (RPTP beta) mediates cell-cell and cell-matrix interactions. By searching for intracellular proteins that interact with the cytoplasmic region of this phosphatase using the two-hybrid method, we identified several proteins containing PDZ domains. One of these proteins, MAGI-3...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00302
更新日期:2003-04-01 00:00:00
abstract::Moving the nucleus to a specific position within the cell is an important event during many cell and developmental processes. Several different molecular mechanisms exist to position nuclei in various cell types. In this Commentary, we review the recent progress made in elucidating mechanisms of nuclear migration in a...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
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更新日期:2016-05-15 00:00:00
abstract::Intermediate filament protein keratin 8 (K8) binds to heat shock protein 70 (Hsp70) and p38 MAPK, and is phosphorylated at Ser74 by p38α (MAPK14, hereafter p38). However, a p38 binding site on K8 and the molecular mechanism of K8-p38 interaction related to Hsp70 are unknown. Here, we identify a p38 docking site on K8 ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.229534
更新日期:2019-09-26 00:00:00
abstract::A key signaling event that is responsible for gradient sensing in eukaryotic cell chemotaxis is a phosphatidylinositol (PtdIns) lipid reaction system. The self-organization activity of this PtdIns lipid system induces an inherent polarity, even in the absence of an external chemoattractant gradient, by producing a loc...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.108373
更新日期:2012-11-01 00:00:00
abstract::The IGF-II mRNA-binding proteins (IMPs), which are composed of two RNA recognition motifs, (RRM) and four hnRNP K homology (KH) domains, have been implicated in subcytoplasmic localization of mRNAs during embryogenesis. The IMP family originated via two gene duplications before the divergence of vertebrates, and IMP h...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-05-15 00:00:00
abstract::Vertebrate tropomyosins (TMs) are expressed from four genes, and at least 18 distinct isoforms are generated via a complex pattern of alternative RNA splicing and alternative promoters. The functional significance of this isoform diversity is largely unknown and it remains to be determined whether specific isoforms ar...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
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abstract::Circadian rhythms exist in most living organisms. The general molecular mechanisms that are used to generate 24-hour rhythms are conserved among organisms, although the details vary. These core clocks consist of multiple regulatory feedback loops, and must be coordinated and orchestrated appropriately for the fine-tun...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
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更新日期:2011-02-01 00:00:00
abstract::Prions are proteins that access self-templating amyloid forms, which confer phenotypic changes that can spread from individual to individual within or between species. These infectious phenotypes can be beneficial, as with yeast prions, or deleterious, as with mammalian prions that transmit spongiform encephalopathies...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.051672
更新日期:2010-04-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::alphaA-Crystallin (alphaA) is a molecular chaperone expressed preferentially in the lens. alphaA transcripts are first detected during the early stages of lens development and its synthesis continues as the lens grows throughout life. alphaA(-/-) mouse lenses are smaller than controls, and lens epithelial cells derive...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00325
更新日期:2003-03-15 00:00:00
abstract::Nedd1 is a new member of the gamma-tubulin ring complex (gammaTuRC) and targets the gammaTuRC to the centrosomes for microtubule nucleation and spindle assembly in mitosis. Although its role is known, its functional regulation mechanism remains unclear. Here we report that the function of Nedd1 is regulated by Cdk1 an...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.042747
更新日期:2009-07-01 00:00:00
abstract::Hepatocyte growth factor, also known as scatter factor, is a pleiotropic cytokine, which stimulates cell motility, invasion, proliferation, survival and morphogenesis, and induces the expression of specific genes by activating its receptor tyrosine kinase. In this work we have isolated, characterized and used as agoni...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Vesicle-vesicle fusion initiated in cell cytoplasm by high Ca(2+) can rapidly erect large membrane boundaries. These might be used as a 'patch' for resealing plasma membrane disruptions. Three central predictions of this 'patch' hypothesis are here established in sea urchin eggs. First, we show that surface markers fo...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::The protozoan parasite Giardia intestinalis (also known as Giardia lamblia) is a major waterborne pathogen. During its life cycle, Giardia alternates between the actively growing trophozoite, which has two diploid nuclei with low levels of allelic heterozygosity, and the infectious cyst, which has four nuclei and a to...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.103879
更新日期:2012-05-15 00:00:00
abstract::Distributions of ErbB receptors on membranes of SKBR3 breast cancer cells were mapped by immunoelectron microscopy. The most abundant receptor, ErbB2, is phosphorylated, clustered and active. Kinase inhibitors ablate ErbB2 phosphorylation without dispersing clusters. Modest co-clustering of ErbB2 and EGFR, even after ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.007658
更新日期:2007-08-15 00:00:00
abstract::Protein kinase CK2, a vital, pleiotropic and highly conserved serine/threonine phosphotransferase is involved in transcription-directed signaling, gene control and cell cycle regulation and is suspected to play a role in global processes. Searching for these global roles, we analyzed the involvement of CK2 in gene exp...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00352
更新日期:2003-04-15 00:00:00
abstract::Plectin, a cytolinker protein greater than 500 kDa in size, has an important role as a mechanical stabiliser of cells. It interlinks the various cytoskeletal filament systems and anchors intermediate filaments to peripheral junctional complexes. In addition, there is increasing evidence that plectin acts as a scaffold...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02891
更新日期:2006-05-01 00:00:00
abstract::Although the 11.5 kDa Zn(2+)-binding protein (ZnBP, parathymosin-alpha) possesses a functional bipartite nuclear localization signal it was found in most tissues in the cytoplasm. The cultivation of freshly isolated rat hepatocytes for 24 hours under standard conditions was associated with an almost complete transloca...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Rab GTPases are key regulators of intracellular trafficking, and cycle between a GTP-bound active state and a GDP-bound inactive state. This cycle is regulated by guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Several efforts have been made in connecting the correct GEFs and GAPs to ...
journal_title:Journal of cell science
pub_type: 杂志文章
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更新日期:2018-09-03 00:00:00
abstract::A myosin heavy chain polypeptide has been identified and localized in Nicotiana pollen tubes using monoclonal anti-myosin antibodies. The epitopes of these antibodies were found to reside on the myosin heavy chain head and rod portion and were, therefore, designated anti-S-1 (myosin S-1) and anti-LMM (light meromyosin...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
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journal_title:Journal of cell science
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journal_title:Journal of cell science
pub_type: 杂志文章
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更新日期:2017-03-15 00:00:00
abstract::Endonuclease G is a mitochondrial protein implicated in DNA fragmentation during apoptosis in cell types ranging from fungi to mammals. Features of programmed cell death have been reported in a number of single-celled organisms, including the human trypanosomatid parasites Leishmania and Trypanosoma. However, the prot...
journal_title:Journal of cell science
pub_type: 杂志文章
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abstract::Mammalian homologs of the Drosophila TRP protein have been shown to form cation-permeable channels in the plasma membrane but very little is known about the mechanisms that control their cell surface localization. Recently it has been demonstrated that the last three C-terminal amino acids (TRL) of TRPC4 comprise a PD...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::Centaurin-alpha(1) is a phosphatidylinositol 3,4,5-trisphosphate binding protein as well as a GTPase activating protein (GAP) for the ADP-ribosylation factor (ARF) family of small GTPases. To further understand its cellular function, we screened a rat brain cDNA library using centaurin-alpha(1) as bait to identify cen...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02369
更新日期:2005-06-01 00:00:00
abstract::Increases in RNA, protein and cell size were determined cytophotometrically during the cell division cycle of Tetrahymena. For these parameters different patterns were found. RNA accumulates slowly during G1 period and faster during macronuclear S. This agrees with the changing uridine incorporation rate which is at l...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract::The nuclear division of Oxyrrhis marina is a very distinct one among the mitoses of dinoflagellates that have been studies. Using synchronized populations, we have investigated the ultrastructural changes in this nuclear division. In interphase, nuclei can be classified into two groups on the basis of the shapes of th...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show, by using frog retinas and recombinant human proteins, that ...
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更新日期:2017-12-01 00:00:00