FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2093317801> ?p ?o ?g. }

• W2093317801 endingPage "1533" @default.
• W2093317801 startingPage "1523" @default.
• W2093317801 abstract "Abstract —Sphingolipids and their metabolic products are now known to have second-messenger functions in a variety of cellular signaling pathways. Lactosylceramide (LacCer), a glycosphingolipid (GSL) present in vascular cells such as endothelial cells, smooth muscle cells, macrophages, neutrophils, platelets, and monocytes, contributes to atherosclerosis. Large amounts of LacCer accumulate in fatty streaks, intimal plaque, and calcified intimal plaque, along with oxidized low density lipoproteins (Ox-LDLs), growth factors, and proinflammatory cytokines. A possible role for LacCer in vascular cell biology was suggested when this GSL was found to stimulate the proliferation in vitro of aortic smooth muscle cells (ASMCs). A further link of LacCer in atherosclerosis was uncovered by the finding that Ox-LDLs stimulated specifically the biosynthesis of LacCer. Ox-LDL–stimulated endogenous synthesis of LacCer by activation of UDP-Gal:GlcCer,β1-4galtransferase (GalT-2) is an early step in this signaling pathway. In turn, LacCer serves as a lipid second messenger that orchestrates a signal transduction pathway, ultimately leading to cell proliferation. This signaling pathway includes LacCer-mediated activation of NADPH oxidase that produces superoxide. Such superoxide molecules stimulate the GTP loading of p21 ras . Subsequently, the kinase cascade (Raf-1, Mek2, and p 44 MAPK [mitogen-activated protein kinase]) is activated. The phosphorylated form of p 44 MAPK translocates from the cytoplasm to the nucleus and engages in c -fos expression, proliferating cell nuclear antigen (PCNA) such as cyclin activation, and cell proliferation takes place. Interestingly, d -threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of GalT-2, can abrogate the Ox-LDL–mediated activation of GalT-2, the signal kinase cascade noted above, as well as cell proliferation. Additional studies have revealed that LacCer mediates the tumor necrosis factor-α (TNF-α)–induced nuclear factor-κB expression and intercellular adhesion molecule (ICAM-1) expression in vascular endothelial cells via the redox-dependent transcriptional pathway. LacCer also stimulates the expression of CD11/CD8, or Mac-1, on the surface of human neutrophils. Collectively, this phenomenon may contribute to the adhesion of neutrophils or monocytes to the endothelial cell surface and thus initiate the process of atherosclerosis. In addition, the LacCer–mediated proliferation of ASMCs may contribute to the progression of atherosclerosis. On the other hand, programmed cell death (apoptosis) by proinflammatory cytokines such as TNF-α, interleukin-1, and high concentrations of Ox-LDL occur via activation of a cell membrane–associated neutral sphingomyelinase (N-SMase). N-SMase hydrolyzes sphingomyelin into ceramide and phosphocholine. In turn, ceramide or a homologue serves as an important stress-signaling molecule. Interestingly, an antibody against N-SMase can abrogate Ox-LDL– and TNF-α–induced apoptosis and therefore may be useful for in vivo studies of apoptosis in experimental animals. Because plaque stability is an integral aspect of atherosclerosis management, activation of N-SMase and subsequent apoptosis may be vital events in the onset of plaque rupture, stroke, or heart failure. Interestingly, in human liver cells, N-SMase action mediates the TNF-α–induced maturation of the sterol regulatory-element binding protein. Moreover, a cell-permeable ceramide can reconstitute the phenomenon above in a sterol-independent fashion. Such findings may provide new avenues for therapy for patients with atherosclerosis. The findings described here indicate an important role for sphingolipids in vascular biology and provide an exciting opportunity for further research in vascular disease and atherosclerosis." @default.
• W2093317801 created "2016-06-24" @default.
• W2093317801 creator A5000104019 @default.
• W2093317801 date "1998-10-01" @default.
• W2093317801 modified "2023-10-12" @default.
• W2093317801 title "Sphingolipids in Atherosclerosis and Vascular Biology" @default.
• W2093317801 cites W1490806866 @default.
• W2093317801 cites W1507272843 @default.
• W2093317801 cites W1516047133 @default.
• W2093317801 cites W1524346733 @default.
• W2093317801 cites W1531986036 @default.
• W2093317801 cites W1551180853 @default.
• W2093317801 cites W1560419760 @default.
• W2093317801 cites W1566441785 @default.
• W2093317801 cites W1566897609 @default.
• W2093317801 cites W1568529372 @default.
• W2093317801 cites W1583264261 @default.
• W2093317801 cites W1583865009 @default.
• W2093317801 cites W1628167280 @default.
• W2093317801 cites W1635474458 @default.
• W2093317801 cites W1734082729 @default.
• W2093317801 cites W1777070967 @default.
• W2093317801 cites W1843461492 @default.
• W2093317801 cites W1846722065 @default.
• W2093317801 cites W1899385764 @default.
• W2093317801 cites W1940973296 @default.
• W2093317801 cites W1974158257 @default.
• W2093317801 cites W1985199555 @default.
• W2093317801 cites W1987162287 @default.
• W2093317801 cites W1989845690 @default.
• W2093317801 cites W1994940574 @default.
• W2093317801 cites W1996192399 @default.
• W2093317801 cites W1998949162 @default.
• W2093317801 cites W1999156442 @default.
• W2093317801 cites W2000823512 @default.
• W2093317801 cites W2005230846 @default.
• W2093317801 cites W2005910570 @default.
• W2093317801 cites W2006415052 @default.
• W2093317801 cites W2008161863 @default.
• W2093317801 cites W2009373735 @default.
• W2093317801 cites W2011495375 @default.
• W2093317801 cites W2020209752 @default.
• W2093317801 cites W2025019624 @default.
• W2093317801 cites W2032786707 @default.
• W2093317801 cites W2034052978 @default.
• W2093317801 cites W2040326609 @default.
• W2093317801 cites W2048569323 @default.
• W2093317801 cites W2057399985 @default.
• W2093317801 cites W2062535842 @default.
• W2093317801 cites W2064638709 @default.
• W2093317801 cites W2072727557 @default.
• W2093317801 cites W2076812453 @default.
• W2093317801 cites W2077128402 @default.
• W2093317801 cites W2077683653 @default.
• W2093317801 cites W2078475812 @default.
• W2093317801 cites W2085114776 @default.
• W2093317801 cites W2086176714 @default.
• W2093317801 cites W2091217736 @default.
• W2093317801 cites W2091992630 @default.
• W2093317801 cites W2094309806 @default.
• W2093317801 cites W2098862614 @default.
• W2093317801 cites W2109662937 @default.
• W2093317801 cites W2117358055 @default.
• W2093317801 cites W2125232915 @default.
• W2093317801 cites W2130902918 @default.
• W2093317801 cites W2134353518 @default.
• W2093317801 cites W2137511741 @default.
• W2093317801 cites W2137570167 @default.
• W2093317801 cites W2155678609 @default.
• W2093317801 cites W2160942082 @default.
• W2093317801 cites W2161188230 @default.
• W2093317801 cites W2166316651 @default.
• W2093317801 cites W2166371391 @default.
• W2093317801 cites W2169565753 @default.
• W2093317801 cites W2183353649 @default.
• W2093317801 cites W2185467543 @default.
• W2093317801 cites W2397318172 @default.
• W2093317801 cites W2514866523 @default.
• W2093317801 cites W304399618 @default.
• W2093317801 doi "https://doi.org/10.1161/01.atv.18.10.1523" @default.
• W2093317801 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9763522" @default.
• W2093317801 hasPublicationYear "1998" @default.
• W2093317801 type Work @default.
• W2093317801 sameAs 2093317801 @default.
• W2093317801 citedByCount "203" @default.
• W2093317801 countsByYear W20933178012012 @default.
• W2093317801 countsByYear W20933178012013 @default.
• W2093317801 countsByYear W20933178012014 @default.
• W2093317801 countsByYear W20933178012015 @default.
• W2093317801 countsByYear W20933178012016 @default.
• W2093317801 countsByYear W20933178012017 @default.
• W2093317801 countsByYear W20933178012018 @default.
• W2093317801 countsByYear W20933178012019 @default.
• W2093317801 countsByYear W20933178012020 @default.
• W2093317801 countsByYear W20933178012021 @default.
• W2093317801 countsByYear W20933178012022 @default.
• W2093317801 countsByYear W20933178012023 @default.
• W2093317801 crossrefType "journal-article" @default.

• next