title: Ascorbic acid prevents increased endothelial permeability caused by oxidized low density lipoprotein.
abstract: Abstract Mildly oxidized low density lipoprotein (mLDL) acutely increases the permeability of the vascular endothelium to molecules that would not otherwise cross the barrier. This study has shown that ascorbic acid tightens the permeability barrier in the endothelial barrier in cells, so this work tested whether it might prevent the increase in endothelial permeability due to mLDL. Treatment of EA.hy926 endothelial cells with mLDL decreased intracellular GSH and activated the cells to further oxidize the mLDL. mLDL also increased endothelial permeability over 2 h to both inulin and ascorbate in cells cultured on semi-permeable filters. This effect was blocked by microtubule and microfilament inhibitors, but not by chelation of intracellular calcium. Intracellular ascorbate both prevented and reversed the mLDL-induced increase in endothelial permeability, an effect mimicked by other cell-penetrant antioxidants. These results suggest a role for endothelial cell ascorbate in ameliorating an important facet of endothelial dysfunction caused by mLDL.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, USA. james.may@vanderbilt.edu
authors.forename: James M
authors.initials: JM
authors.lastname: May
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Qu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D001205:Ascorbic Acid
references.citation: J Cell Physiol. 1995 May;163(2):393-9
references.pmid: 7706381
references.citation: J Cell Physiol. 1987 Jul;132(1):111-7
references.pmid: 3597548
references.citation: Arch Biochem Biophys. 2005 Feb 1;434(1):178-86
references.pmid: 15629121
references.citation: Arterioscler Thromb Vasc Biol. 1997 Aug;17(8):1583-90
references.pmid: 9301639
references.citation: Cardiovasc Res. 2009 May 1;82(2):371-81
references.pmid: 19176597
references.citation: Circ Res. 1997 Jan;80(1):37-44
references.pmid: 8978320
references.citation: N Engl J Med. 1989 Apr 6;320(14):915-24
references.pmid: 2648148
references.citation: J Biol Chem. 1999 Oct 22;274(43):30361-4
references.pmid: 10521411
references.citation: Mol Cell Biochem. 2008 Feb;309(1-2):125-32
references.pmid: 18026819
references.citation: J Cell Physiol. 1996 Jun;167(3):562-9
references.pmid: 8655610
references.citation: Am J Physiol Cell Physiol. 2009 Jul;297(1):C169-78
references.pmid: 19419995
references.citation: Arch Biochem Biophys. 1998 Jan 15;349(2):281-9
references.pmid: 9448716
references.citation: Free Radic Biol Med. 2009 Apr 15;46(8):1049-57
references.pmid: 19185609
references.citation: Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2305-11
references.pmid: 7489257
references.citation: Arterioscler Thromb Vasc Biol. 1997 Aug;17(8):1575-82
references.pmid: 9301638
references.citation: Free Radic Biol Med. 1999 Sep;27(5-6):667-72
references.pmid: 10490287
references.citation: Biochem Pharmacol. 2001 Oct 1;62(7):873-81
references.pmid: 11543722
references.citation: Free Radic Biol Med. 2002 Jul 1;33(1):83-93
references.pmid: 12086686
references.citation: Free Radic Biol Med. 1995 Aug;19(2):177-87
references.pmid: 7649489
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: J Biol Chem. 1998 Aug 21;273(34):21867-74
references.pmid: 9705325
references.citation: FEBS Lett. 1992 Mar 24;299(1):60-5
references.pmid: 1544476
references.citation: Anal Biochem. 1976 Jul;74(1):214-26
references.pmid: 962076
references.citation: Circ Res. 2007 May 11;100(9):1337-43
references.pmid: 17446432
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6931-6
references.pmid: 10359816
references.citation: J Neurochem. 1997 Mar;68(3):991-1000
references.pmid: 9048744
references.citation: Eur J Clin Invest. 1997 Jan;27(1):48-54
references.pmid: 9041377
references.citation: FEBS Lett. 2010 Jan 4;584(1):61-6
references.pmid: 19944695
references.citation: Arch Biochem Biophys. 2009 May 15;485(2):174-82
references.pmid: 19254685
references.citation: Am J Physiol Cell Physiol. 2001 Apr;280(4):C719-41
references.pmid: 11245588
references.citation: Mol Cell Biochem. 2009 May;325(1-2):79-88
references.pmid: 19148707
references.citation: Biochem Pharmacol. 1994 May 18;47(10):1725-30
references.pmid: 8204089
references.citation: J Cell Biol. 2007 Feb 26;176(5):719-27
references.pmid: 17312022
references.citation: J Cell Physiol. 1992 Dec;153(3):437-49
references.pmid: 1280276
references.citation: Microvasc Res. 2004 Nov;68(3):231-8
references.pmid: 15501242
references.citation: Proc Natl Acad Sci U S A. 1984 Jun;81(12):3883-7
references.pmid: 6587396
references.citation: Experientia. 1996 Mar 15;52(3):234-8
references.pmid: 8631392
references.citation: Biol Trace Elem Res. 1995 Jan-Mar;47(1-3):81-91
references.pmid: 7779579
references.citation: Am J Hematol. 1995 Jul;49(3):250-2
references.pmid: 7604820
references.citation: J Biol Chem. 1970 Mar 25;245(6):1374-7
references.pmid: 5462997