title: Cyp1b1 mediates periostin regulation of trabecular meshwork development by suppression of oxidative stress.
abstract: Mutation in CYP1B1 has been reported for patients with congenital glaucoma. However, the underlying mechanisms remain unknown. Here we show increased diurnal intraocular pressure (IOP) in Cyp1b1-deficient (Cyp1b1(-/-)) mice. Cyp1b1(-/-) mice presented ultrastructural irregular collagen distribution in their trabecular meshwork (TM) tissue along with increased oxidative stress and decreased levels of periostin (Postn). Increased levels of oxidative stress and decreased levels of Postn were also detected in human glaucomatous TM tissues. Furthermore, Postn-deficient mice exhibited TM tissue ultrastructural abnormalities similar to those of Cyp1b1(-/-) mice. Administration of the antioxidant N-acetylcysteine (NAC) restored structural abnormality of TM tissue in Cyp1b1(-/-) mice. In addition, TM cells prepared from Cyp1b1(-/-) mice exhibited increased oxidative stress, altered adhesion, and decreased levels of Postn. These aberrant cellular responses were reversed in the presence of NAC or by restoration of Cyp1b1 expression. Cyp1b1 knockdown or inhibition of CYP1B1 activity in Cyp1b1(+/+) TM cells resulted in a Cyp1b1(-/-) phenotype. Thus, metabolic activity of CYP1B1 contributes to oxidative homeostasis and ultrastructural organization and function of TM tissue through modulation of Postn expression.
authors: Departments of Ophthalmology and Visual Sciences.
authors: Yun
authors: Y
authors: Zhao
authors: Shoujian
authors: S
authors: Wang
authors: Christine M
authors: CM
authors: Sorenson
authors: Leandro
authors: L
authors: Teixeira
authors: Richard R
authors: RR
authors: Dubielzig
authors: Donna M
authors: DM
authors: Peters
authors: Simon J
authors: SJ
authors: Conway
authors: Colin R
authors: CR
authors: Jefcoate
authors: Nader
authors: N
authors: Sheibani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D014129:Trabecular Meshwork / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D024022:Fibrillar Collagens; C082838:Postn protein, mouse; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1
references: Am J Ophthalmol. 1979 Sep;88(3 Pt 1):424-6
references: 484670
references: Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1803-11
references: 11431445
references: J Clin Endocrinol Metab. 1985 Jan;60(1):114-9
references: 3964785
references: Invest Ophthalmol Vis Sci. 2011 Feb 22;52(2):858-64
references: 20720229
references: Am J Physiol Cell Physiol. 2007 Jun;292(6):C2070-83
references: 17563397
references: Lancet. 2004 May 22;363(9422):1711-20
references: 15158634
references: Invest Ophthalmol Vis Sci. 2012 Sep 28;53(10):6708-17
references: 22930728
references: Physiol Rev. 2004 Oct;84(4):1155-228
references: 15383650
references: Exp Eye Res. 2009 Jun 15;89(1):95-100
references: 19268465
references: Invest Ophthalmol Vis Sci. 2012 May 04;53(5):2470-2
references: 22562843
references: Cancer Res. 2001 Nov 15;61(22):8164-70
references: 11719446
references: J Exp Med. 2008 Feb 18;205(2):295-303
references: 18208976
references: Am J Physiol Cell Physiol. 2010 Dec;299(6):C1468-84
references: 20810911
references: Curr Eye Res. 1991 Nov;10(11):1015-30
references: 1782800
references: Prog Retin Eye Res. 2005 Sep;24(5):612-37
references: 15919228
references: Curr Opin Ophthalmol. 1998 Apr;9(2):46-9
references: 10180513
references: Curr Opin Ophthalmol. 2006 Apr;17(2):168-74
references: 16552252
references: Hum Mol Genet. 1997 Apr;6(4):641-7
references: 9097971
references: Drug Metab Dispos. 2005 Apr;33(4):489-94
references: 15616152
references: Invest Ophthalmol Vis Sci. 2012 May 04;53(5):2473-5
references: 22562844
references: Development. 2007 Apr;134(7):1369-83
references: 17329364
references: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):619-23
references: 10711672
references: J Biol Chem. 1994 May 27;269(21):14905-11
references: 8195121
references: Trends Pharmacol Sci. 2005 Aug;26(8):412-9
references: 15992934
references: Exp Cell Res. 1996 Mar 15;223(2):250-8
references: 8601401
references: Am J Hum Genet. 2002 Feb;70(2):448-60
references: 11774072
references: Invest Ophthalmol Vis Sci. 2002 May;43(5):1358-66
references: 11980847
references: Exp Eye Res. 2004 Jul;79(1):61-74
references: 15183101
references: Mol Pharmacol. 1998 Nov;54(5):825-33
references: 9804617
references: J Cell Physiol. 2004 Jul;200(1):45-52
references: 15137056
references: Mol Vis. 2004 Aug 30;10:629-36
references: 15359218
references: Science. 1997 Jan 31;275(5300):668-70
references: 9005853
references: Ophthalmology. 1984 Jun;91(6):580-95
references: 6540429
references: Arch Ophthalmol. 1963 Apr;69:455-67
references: 14012265
references: Nature. 1995 Apr 13;374(6523):643-6
references: 7715704
references: PLoS Genet. 2011 Feb;7(2):e1001306
references: 21379321
references: Pharmacogenetics. 2001 Dec;11(9):793-801
references: 11740343
references: Annu Rev Pharmacol Toxicol. 2005;45:1-25
references: 15832443
references: Carcinogenesis. 1997 Feb;18(2):391-7
references: 9054634
references: Mol Vis. 2003 Jul 03;9:308-14
references: 12847420
references: Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3771-7
references: 19168904
references: Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1392-403
references: 10359321
references: Science. 2003 Mar 7;299(5612):1578-81
references: 12624268
references: BMC Genet. 2001;2:12
references: 11532192
references: Circ Res. 2008 Apr 11;102(7):752-60
references: 18296617
references: Am J Physiol Renal Physiol. 2012 Apr 1;302(7):F809-19
references: 22169007
references: Exp Eye Res. 2012 Jun;99:27-35
references: 22554836
references: Exp Eye Res. 2006 Jun;82(6):959-67
references: 16310191
references: J Glaucoma. 2003 Feb;12(1):27-30
references: 12567107
references: Br J Ophthalmol. 2006 Mar;90(3):262-7
references: 16488940
references: Exp Eye Res. 2009 Apr;88(4):738-46
references: 19084518
references: Exp Eye Res. 2010 Dec;91(6):901-8
references: 20932969
references: Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1581-5
references: 12657595
references: Exp Eye Res. 2009 Apr;88(4):769-75
references: 19114037
references: J Cell Physiol. 1999 Aug;180(2):182-9
references: 10395288
references: Mol Vis. 2003 May 01;9:171-8
references: 12740568
references: Drug Metab Dispos. 2007 Jun;35(6):987-94
references: 17325023
references: J Urol. 2011 Oct;186(4):1537-44
references: 21855915
references: Exp Eye Res. 2008 Oct;87(4):376-84
references: 18674535
references: Invest Ophthalmol Vis Sci. 2002 Jan;43(1):151-61
references: 11773026
references: Invest Ophthalmol Vis Sci. 2012 Mar 21;53(3):1566-75
references: 22297497
references: J Cell Biochem. 2007 Jun 1;101(3):695-711
references: 17226767
references: Invest Ophthalmol Vis Sci. 2005 Jan;46(1):183-90
references: 15623772
references: Mol Cell Biol. 2005 Dec;25(24):11131-44
references: 16314533
references: Invest Ophthalmol Vis Sci. 1992 Feb;33(2):424-9
references: 1740375
references: Hum Mol Genet. 2000 Apr 12;9(7):1021-32
references: 10767326
references: BMC Genet. 2001;2:18
references: 11722794
references: Free Radic Biol Med. 1991;11(1):81-128
references: 1937131
references: J Biol Chem. 1994 May 6;269(18):13092-9
references: 8175734
references: Blood. 2009 Jan 15;113(3):744-54
references: 19005183
references: J Comp Neurol. 1999 Mar 15;405(3):394-405
references: 10076934
references: Drug Metab Dispos. 2004 Aug;32(8):840-7
references: 15258110
references: J Glaucoma. 2001 Oct;10(5 Suppl 1):S42-4
references: 11890273
references: Exp Eye Res. 2009 Apr;88(4):648-55
references: 19239914
references: Invest Ophthalmol Vis Sci. 2003 Feb;44(2):473-85
references: 12556371
references: Cell Tissue Res. 2007 Oct;330(1):133-45
references: 17602244
references: Exp Eye Res. 2009 Apr;88(4):713-7
references: 18793636
references: J Bone Miner Res. 1999 Jul;14(7):1239-49
references: 10404027
references: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):765-70
references: 18936135