title: The mPlrp2 and mClps genes are involved in the hydrolysis of retinyl esters in the mouse liver.
abstract: Retinyl esters are the major chemical forms of vitamin A stored in the liver, and can be delivered to peripheral tissues for conversion into biologically active forms. The function and regulation of the hepatic genes that are potentially involved in catalyzing the hydrolysis of retinyl esters remain unclear. Here we show that two lipid hydrolytic genes, pancreatic-related protein 2 (mPlrp2) and procolipase (mClps), expressed specifically in the mouse pancreas, are associated with the ratio of S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy). Light illumination deficiency or administration of 5'-AMP elevated the ratio of AdoMet to AdoHcy and induced the expression in the liver of mPlrp2 and mClps, which was blocked by all-trans retinoic acid. Mice fed a vitamin A-free diet exhibited increased activation of hepatic mPlrp2 and mClps expression, which was associated with increased methylation of histone H3K4 residues located near the mPlrp2 and mClps promoters. Inhibition of hepatic mPlrp2 and mClps expression by a methylase inhibitor, methylthioadenosine, markedly decreased plasma retinol levels in these mice. The activated hepatic stellate cell (HSC)-T6 cell line specifically expressed mClps and mPlrp2. Inhibition of mClps gene expressions by short hairpin RNA (shRNA) decreased hydrolysis of retinyl esters in the HSC-T6 cell line. These data suggest that the conditional expression of mPlrp2 and mClps is involved in the hydrolysis of retinyl esters in the mouse liver.
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, 210094, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Pang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shiming
authors.initials: S
authors.lastname: Wang
authors.forename: Aiqun
authors.initials: A
authors.lastname: Jia
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Chun
authors.initials: C
authors.lastname: Cai
authors.forename: Zichun
authors.initials: Z
authors.lastname: Hua
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D002851:Chromatography, High Pressure Liquid; D003089:Colipases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D004952:Esters / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D003089:Colipases; D004792:Enzyme Precursors; D004952:Esters; D014212:Tretinoin; C037107:procolipase; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008049:Lipase; C075988:pancreatic lipase related protein 2