title: Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung.
abstract: Vitamin A (VA) is essential for fetal lung development and postnatal lung maturation. VA is stored mainly as retinyl esters (REs), which may be mobilized for production of retinoic acid (RA). This study was designed 1) to evaluate several acidic retinoids for their potential to increase RE in the lungs of VA-supplemented neonatal rats, and 2) to determine the expression of retinoid homeostatic genes related to retinol uptake, esterification, and catabolism as possible mechanisms. When neonatal rats were treated with VA combined with any one of several acidic retinoids (RA, 9-cis-RA, or Am580, a stable analog of RA), lung RE increased approximately 5-7 times more than after an equal amount of VA alone. Retinol uptake and esterification during the period of absorption correlated with increased expression of both STRA6 (retinol-binding protein receptor) and LRAT (retinol esterification), while a reduction in RE after 12 h in Am580-treated, VA-supplemented rats correlated with a strong and persistent increase in CYP26B1 (RA hydroxylase). We conclude that neonatal lung RE can be increased synergistically by VA combined with both natural and synthetic acidic retinoids, concomitant with induction of the dyad of STRA6 and LRAT. However, the pronounced and prolonged induction of CYP26B1 by Am580 may counteract lung RE accumulation after the absorption process is completed.
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Wu
authors.forename: A Catharine
authors.initials: AC
authors.lastname: Ross
mesh_terms: D000042:Absorption / Q000187:drug effects; D000217:Acyltransferases / Q000235:genetics*; D000077556:Alitretinoin; D000818:Animals; D000831:Animals, Newborn; D001565:Benzoates / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004357:Drug Synergism; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072516:Retinoic Acid 4-Hydroxylase; D012176:Retinoids / Q000737:chemistry / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001565:Benzoates; D004952:Esters; D008565:Membrane Proteins; D012176:Retinoids; C547866:STRA6 protein, rat; D013764:Tetrahydronaphthalenes; C068073:Am 580; D014801:Vitamin A; D000077556:Alitretinoin; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase
references.citation: FASEB J. 2000 Oct;14(13):2119-27
references.pmid: 11023996
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L431-3
references.pmid: 12533315
references.citation: Biochem J. 2005 Nov 15;392(Pt 1):241-8
references.pmid: 16053444
references.citation: J Lipid Res. 2000 Dec;41(12):2024-34
references.pmid: 11108736
references.citation: J Biol Chem. 1991 Sep 5;266(25):16453-7
references.pmid: 1885578
references.citation: FASEB J. 1996 Jul;10(9):986-92
references.pmid: 8801181
references.citation: J Nutr. 2003 Jan;133(1):291S-296S
references.pmid: 12514312
references.citation: Am J Hum Genet. 2007 Mar;80(3):550-60
references.pmid: 17273977
references.citation: J Am Acad Dermatol. 2001 Nov;45(5):S136-42
references.pmid: 11606945
references.citation: Gene. 2004 Mar 17;328:1-16
references.pmid: 15019979
references.citation: Biol Neonate. 1990;58(6):318-25
references.pmid: 2288994
references.citation: J Nutr. 2006 Nov;136(11):2803-7
references.pmid: 17056804
references.citation: Curr Opin Gastroenterol. 2001 Mar;17(2):184-192
references.pmid: 11224677
references.citation: Dev Biol. 1995 Aug;170(2):420-33
references.pmid: 7649373
references.citation: Pediatrics. 2005 Mar;115(3):e249-54
references.pmid: 15713907
references.citation: Arch Dis Child Fetal Neonatal Ed. 2005 Mar;90(2):F103-8
references.pmid: 15724031
references.citation: N Engl J Med. 1999 Jun 24;340(25):1962-8
references.pmid: 10379020
references.citation: Am J Clin Nutr. 2005 Apr;81(4):851-8
references.pmid: 15817863
references.citation: Am J Respir Cell Mol Biol. 2000 Aug;23(2):162-7
references.pmid: 10919981
references.citation: J Nutr. 1997 Feb;127(2):218-24
references.pmid: 9039821
references.citation: Proc Am Thorac Soc. 2006 Nov;3(8):709-12
references.pmid: 17065378
references.citation: J Pediatr. 2003 Jun;142(6):656-61
references.pmid: 12838194
references.citation: Arch Biochem Biophys. 1997 Aug 1;344(1):220-7
references.pmid: 9244401
references.citation: J Pediatr. 1981 Aug;99(2):302-5
references.pmid: 7195934
references.citation: J Perinat Med. 1993;21(1):59-62
references.pmid: 8487152
references.citation: J Biol Chem. 1957 May;226(1):497-509
references.pmid: 13428781
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4879-84
references.pmid: 8643497
references.citation: J Lipid Res. 1987 Aug;28(8):973-81
references.pmid: 3668391
references.citation: Am J Physiol. 1996 Feb;270(2 Pt 1):L305-10
references.pmid: 8780001
references.citation: Chest. 2002 May;121(5 Suppl):206S-208S
references.pmid: 12010853
references.citation: Methods Enzymol. 1986;123:68-74
references.pmid: 3702743
references.citation: Life Sci. 2005 Feb 18;76(14):1613-22
references.pmid: 15680170
references.citation: Biochem Biophys Res Commun. 1990 Feb 14;166(3):1300-7
references.pmid: 2154975
references.citation: Science. 2007 Feb 9;315(5813):820-5
references.pmid: 17255476
references.citation: Arch Biochem Biophys. 2002 May 15;401(2):235-43
references.pmid: 12054474
references.citation: J Pediatr. 1992 Sep;121(3):399-401
references.pmid: 1517914
references.citation: J Pediatr. 1996 Apr;128(4):489-96
references.pmid: 8618182
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L249-56
references.pmid: 12832282
references.citation: Philos Trans R Soc Lond B Biol Sci. 2004 May 29;359(1445):799-808
references.pmid: 15293808
references.citation: J Pediatr. 1987 Aug;111(2):269-77
references.pmid: 3302193
references.citation: Biol Neonate. 1987;52(1):48-60
references.pmid: 3620554
references.citation: Chest. 2000 May;117(5 Suppl 1):235S-41S
references.pmid: 10843926
references.citation: J Biol Chem. 1985 May 10;260(9):5228-31
references.pmid: 3988751
references.citation: Pediatr Pulmonol. 2005 Aug;40(2):113-34
references.pmid: 15965895
references.citation: Annu Rev Physiol. 2000;62:825-46
references.pmid: 10845113
references.citation: J Lipid Res. 1982 Jan;23(1):133-44
references.pmid: 7057102
references.citation: J Natl Cancer Inst. 1993 Dec 1;85(23):1921-6
references.pmid: 8230282
references.citation: J Nutr. 2000 May;130(5):1159-65
references.pmid: 10801913
references.citation: Semin Perinatol. 2006 Jun;30(3):121-8
references.pmid: 16813970
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L345-58
references.pmid: 11839527
references.citation: Am J Physiol. 1994 Jun;266(6 Pt 1):L705-12
references.pmid: 8023960
references.citation: Eur Respir J. 2004 Jan;23(1):20-7
references.pmid: 14738226
references.citation: BMJ. 2003 Aug 2;327(7409):254
references.pmid: 12896935
references.citation: Biol Neonate. 1990;57(2):126-32
references.pmid: 2310790
references.citation: Curr Med Chem. 2002 Mar;9(5):591-608
references.pmid: 11945126
references.citation: Mech Dev. 1997 May;63(2):173-86
references.pmid: 9203140
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L468-76
references.pmid: 11839540
references.citation: J Lipid Res. 2006 Aug;47(8):1844-51
references.pmid: 16685080
references.citation: J Nutr. 2005 Apr;135(4):746-52
references.pmid: 15795428