title: Post-translational modifications, a key process in CD36 function: lessons from the spontaneously hypertensive rat heart.
abstract: CD36, a multifunctional protein, is involved in cardiac long chain fatty acid (LCFA) metabolism and in the etiology of heart diseases, yet the functional impact of Cd36 gene variants remains unclear. In 7-week-old spontaneously hypertensive rats (SHR), which, like humans, carry numerous mutations in Cd36, we tested the hypothesis that their restricted cardiac LCFA utilization occurs prior to hypertrophy due to defective CD36 post-translational modifications (PTM), as assessed by ex vivo perfusion of (13)C-labeled substrates and biochemical techniques. Compared to their controls, SHR hearts displayed a lower (i) contribution of LCFA to β-oxidation (-40%) and triglycerides (+2.8 folds), which was not explained by transcriptional changes or malonyl-CoA level, a recognized β-oxidation inhibitor, and (ii) membrane-associated CD36 protein level, but unchanged distribution. Other results demonstrate alterations in CD36 PTM in SHR hearts, specifically by N-glycosylation, and the importance of O-linked-β-N-acetylglucosamine for its membrane recruitment and role in LCFA use in the heart.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Quebec H1T 1C8, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lauzier
authors.forename: Clémence
authors.initials: C
authors.lastname: Merlen
authors.forename: Fanny
authors.initials: F
authors.lastname: Vaillant
authors.forename: Janie
authors.initials: J
authors.lastname: McDuff
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bouchard
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Beguin
authors.forename: Vernon W
authors.initials: VW
authors.lastname: Dolinsky
authors.forename: Sylvain
authors.initials: S
authors.lastname: Foisy
authors.forename: Louis R
authors.initials: LR
authors.lastname: Villeneuve
authors.forename: François
authors.initials: F
authors.lastname: Labarthe
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Allen
authors.forename: Guy
authors.initials: G
authors.lastname: Charron
authors.forename: Christine
authors.initials: C
authors.lastname: Des Rosiers
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D015151:Immunoblotting; D008316:Malonyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D005227:Fatty Acids; D006023:Glycoproteins; D014280:Triglycerides; D008316:Malonyl Coenzyme A