Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung.
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.
Wu
Lili
L
Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Ross
A Catharine
AC
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*
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
FASEB J. 2000 Oct;14(13):2119-27
11023996
Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L431-3
12533315
Biochem J. 2005 Nov 15;392(Pt 1):241-8
16053444
J Lipid Res. 2000 Dec;41(12):2024-34
11108736
J Biol Chem. 1991 Sep 5;266(25):16453-7
1885578
FASEB J. 1996 Jul;10(9):986-92
8801181
J Nutr. 2003 Jan;133(1):291S-296S
12514312
Am J Hum Genet. 2007 Mar;80(3):550-60
17273977
J Am Acad Dermatol. 2001 Nov;45(5):S136-42
11606945
Gene. 2004 Mar 17;328:1-16
15019979
Biol Neonate. 1990;58(6):318-25
2288994
J Nutr. 2006 Nov;136(11):2803-7
17056804
Curr Opin Gastroenterol. 2001 Mar;17(2):184-192
11224677
Dev Biol. 1995 Aug;170(2):420-33
7649373
Pediatrics. 2005 Mar;115(3):e249-54
15713907
Arch Dis Child Fetal Neonatal Ed. 2005 Mar;90(2):F103-8
15724031
N Engl J Med. 1999 Jun 24;340(25):1962-8
10379020
Am J Clin Nutr. 2005 Apr;81(4):851-8
15817863
Am J Respir Cell Mol Biol. 2000 Aug;23(2):162-7
10919981
J Nutr. 1997 Feb;127(2):218-24
9039821
Proc Am Thorac Soc. 2006 Nov;3(8):709-12
17065378
J Pediatr. 2003 Jun;142(6):656-61
12838194
Arch Biochem Biophys. 1997 Aug 1;344(1):220-7
9244401
J Pediatr. 1981 Aug;99(2):302-5
7195934
J Perinat Med. 1993;21(1):59-62
8487152
J Biol Chem. 1957 May;226(1):497-509
13428781
Proc Natl Acad Sci U S A. 1996 May 14;93(10):4879-84
8643497
J Lipid Res. 1987 Aug;28(8):973-81
3668391
Am J Physiol. 1996 Feb;270(2 Pt 1):L305-10
8780001
Chest. 2002 May;121(5 Suppl):206S-208S
12010853
Methods Enzymol. 1986;123:68-74
3702743
Life Sci. 2005 Feb 18;76(14):1613-22
15680170
Biochem Biophys Res Commun. 1990 Feb 14;166(3):1300-7
2154975
Science. 2007 Feb 9;315(5813):820-5
17255476
Arch Biochem Biophys. 2002 May 15;401(2):235-43
12054474
J Pediatr. 1992 Sep;121(3):399-401
1517914
J Pediatr. 1996 Apr;128(4):489-96
8618182
Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L249-56
12832282
Philos Trans R Soc Lond B Biol Sci. 2004 May 29;359(1445):799-808
15293808
J Pediatr. 1987 Aug;111(2):269-77
3302193
Biol Neonate. 1987;52(1):48-60
3620554
Chest. 2000 May;117(5 Suppl 1):235S-41S
10843926
J Biol Chem. 1985 May 10;260(9):5228-31
3988751
Pediatr Pulmonol. 2005 Aug;40(2):113-34
15965895
Annu Rev Physiol. 2000;62:825-46
10845113
J Lipid Res. 1982 Jan;23(1):133-44
7057102
J Natl Cancer Inst. 1993 Dec 1;85(23):1921-6
8230282
J Nutr. 2000 May;130(5):1159-65
10801913
Semin Perinatol. 2006 Jun;30(3):121-8
16813970
Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L345-58
11839527
Am J Physiol. 1994 Jun;266(6 Pt 1):L705-12
8023960
Eur Respir J. 2004 Jan;23(1):20-7
14738226
BMJ. 2003 Aug 2;327(7409):254
12896935
Biol Neonate. 1990;57(2):126-32
2310790
Curr Med Chem. 2002 Mar;9(5):591-608
11945126
Mech Dev. 1997 May;63(2):173-86
9203140
Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L468-76
11839540
J Lipid Res. 2006 Aug;47(8):1844-51
16685080
J Nutr. 2005 Apr;135(4):746-52
15795428