title: ApoO, a novel apolipoprotein, is an original glycoprotein up-regulated by diabetes in human heart.
abstract: Obesity is an independent risk factor for cardiac failure. Obesity promotes excessive deposition of fat in adipose and nonadipose tissues. Intramyocardial lipid overload is a relatively common finding in nonischemic heart failure, especially in obese and diabetic patients, and promotes lipoapoptosis that contributes to the alteration of cardiac function. Lipoprotein production has been proposed as a heart-protective mechanism through the unloading of surplus cellular lipids. We previously analyzed the heart transcriptome in a dog nutritional model of obesity, and we identified a new apolipoprotein, regulated by obesity in heart, which is the subject of this study. We detected this new protein in the following lipoproteins: high density lipoprotein, low density lipoprotein, and very low density lipoprotein. We designated it apolipoprotein O. Apolipoprotein O is a 198-amino acid protein that contains a 23-amino acidlong signal peptide. The apolipoprotein O gene is expressed in a set of human tissues. Confocal immunofluorescence microscopy colocalized apolipoprotein O and perilipins, a cellular marker of the lipid droplet. Chondroitinase ABC deglycosylation analysis or cell incubation with p-nitrophenyl-beta-d-xyloside indicated that apolipoprotein O belongs to the proteoglycan family. Naringenin or CP-346086 treatments indicated that apolipoprotein O secretion requires microsomal triglyceride transfer protein activity. Apolipoprotein O gene expression is up-regulated in the human diabetic heart. Apolipoprotein O promoted cholesterol efflux from macrophage cells. To our knowledge, apolipoprotein O is the first chondroitin sulfate chain containing apolipoprotein. Apolipoprotein O may be involved in myocardium-protective mechanisms against lipid accumulation, or it may have specific properties mediated by its unique glycosylation pattern.
authors.affiliation: Unité de Recherches sur les Obésités, INSERM UPS U586, Institut Louis Bugnard IFR31, CHU Rangueil, Batiment L3, BP 84225, 31432 Toulouse Cedex 4, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lamant
authors.forename: Fatima
authors.initials: F
authors.lastname: Smih
authors.forename: Romain
authors.initials: R
authors.lastname: Harmancey
authors.forename: Pierre
authors.initials: P
authors.lastname: Philip-Couderc
authors.forename: Atul
authors.initials: A
authors.lastname: Pathak
authors.forename: Jerome
authors.initials: J
authors.lastname: Roncalli
authors.forename: Michel
authors.initials: M
authors.lastname: Galinier
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.forename: Pierre
authors.initials: P
authors.lastname: Massabuau
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Senard
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouet
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D019765:Chondroitin ABC Lyase / Q000737:chemistry; D003920:Diabetes Mellitus / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008074:Lipoproteins / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014230:Triazoles / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C000589295:APOO protein, human; D001053:Apolipoproteins; C493884:CP-346086; D044950:Flavanones; D006023:Glycoproteins; D007546:Isoquinolines; D008074:Lipoproteins; D014230:Triazoles; D019765:Chondroitin ABC Lyase; C005273:naringenin