title: The role of cholesterol in UV light B-induced apoptosis.
abstract: Modification of major lipid raft components, such as cholesterol and ceramide, plays a role in regulation of programmed cell death under various stimuli. However, the relationship between cholesterol level modification and the activation of apoptotic signaling cascades upon UVB light has not been established. In this report, we demonstrate that upon UVB irradiation cholesterol levels in membrane rafts of skin cells increase, which leads to Fas-receptor (Fas) aggregation in the rafts. Utilizing a continuous velocity floatation technique, we show that Fas accumulated in the lipid rafts of human melanoma M624 cells after UVB irradiation. The subsequent events of death-inducing signaling complex formation were also detected in the lipid raft fractions. Depletion of cholesterol by methyl-β-cyclodextrin reduces Fas aggregation, while overloading increases. Disruption of lipid rafts also prevents Fas death domain-associated protein (Daxx) from dissociating from Fas in the lipid rafts, which is accompanied with a reduced apoptotic, but increased nonapoptotic death of UVB-irradiated human keratinocytes, HaCaT cells. Results indicate that cholesterol located in the plasma membrane of skin cells is required for lipid raft domain formation and activation of UVB-induced apoptosis.
authors.affiliation: Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH, USA.
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: George
authors.forename: Walid
authors.initials: W
authors.lastname: Elyassaki
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D056970:Co-Repressor Proteins; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects; D008545:Melanoma / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D021962:Membrane Microdomains / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D047392:beta-Cyclodextrins / Q000494:pharmacology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D047392:beta-Cyclodextrins; D019014:fas Receptor; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol
references.citation: Biochem Biophys Res Commun. 2002 Oct 4;297(4):876-9
references.pmid: 12359234
references.citation: J Immunol. 2002 Apr 15;168(8):4095-102
references.pmid: 11937569
references.citation: Neoplasia. 2002 Nov-Dec;4(6):486-92
references.pmid: 12407442
references.citation: J Cell Biol. 1998 Jan 12;140(1):171-82
references.pmid: 9425165
references.citation: Photochem Photobiol. 2006 May-Jun;82(3):787-92
references.pmid: 16438619
references.citation: J Photochem Photobiol B. 2003 Jan;69(1):7-12
references.pmid: 12547491
references.citation: J Clin Rheumatol. 2004 Jun;10(3):143-6
references.pmid: 17043489
references.citation: J Immunol. 1998 Jul 1;161(1):241-51
references.pmid: 9647230
references.citation: Exp Dermatol. 2005 Apr;14(4):266-72
references.pmid: 15810884
references.citation: Annu Rev Cell Dev Biol. 1998;14:111-36
references.pmid: 9891780
references.citation: Immunology. 2002 Oct;107(2):176-82
references.pmid: 12383196
references.citation: Exp Cell Res. 2004 Apr 15;295(1):102-18
references.pmid: 15051494
references.citation: J Immunol. 2004 Aug 1;173(3):1876-86
references.pmid: 15265920
references.citation: Mol Cell Biol. 2002 Jan;22(1):207-20
references.pmid: 11739735
references.citation: J Biol Chem. 1997 Oct 10;272(41):25783-6
references.pmid: 9325306
references.citation: Leukemia. 2010 Jan;24(1):141-52
references.pmid: 19907441
references.citation: Exp Cell Res. 1997 May 1;232(2):255-62
references.pmid: 9168800
references.citation: Biochim Biophys Acta. 2005 Dec 30;1746(3):260-73
references.pmid: 15951036
references.citation: Ukr Biokhim Zh. 1976 Jan-Feb;48(1):86-8
references.pmid: 1258165
references.citation: Cell Struct Funct. 2008;33(1):123-32
references.pmid: 18388398
references.citation: Blood. 2003 May 1;101(9):3628-34
references.pmid: 12506040
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G965-76
references.pmid: 18755811
references.citation: Nat Immunol. 2004 Feb;5(2):182-9
references.pmid: 14745445
references.citation: Arch Dermatol Res. 1991;283(3):191-7
references.pmid: 1867482
references.citation: J Biochem Mol Toxicol. 2004;18(1):50-9
references.pmid: 14994280
references.citation: J Biol Chem. 2001 Aug 17;276(33):30729-36
references.pmid: 11406621
references.citation: Biotechniques. 2010 Nov;49(5):837-8
references.pmid: 21091450
references.citation: Genes Cells. 2004 Sep;9(9):801-9
references.pmid: 15330857
references.citation: Cell Signal. 2006 Jul;18(7):1017-30
references.pmid: 16236485
references.citation: Immunity. 2010 Feb 26;32(2):214-26
references.pmid: 20137986
references.citation: Cell Cycle. 2004 Jun;3(6):725-8
references.pmid: 15197344
references.citation: Leuk Lymphoma. 2011 Jul;52(7):1290-301
references.pmid: 21699383
references.citation: Biochem J. 2004 Mar 1;378(Pt 2):281-92
references.pmid: 14662007