title: The effect of albumin on podocytes: the role of the fatty acid moiety and the potential role of CD36 scavenger receptor.
abstract: Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA+FA) or depleted of them (HSA-FA). Receptor-mediated endocytosis of FITC-HSA+FA over 60 min was 5 times greater than that of FITC-HSA-FA. 24h exposure of podocytes to albumin up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA-FA. Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin.
authors.affiliation: Department of Infection, Immunity and inflammation, University of Leicester, Leicester, UK; John Walls Renal Unit, Leicester General Hospital Leicester, UK. Electronic address: izap1@le.ac.uk.
authors.forename: I Z A
authors.initials: IZ
authors.lastname: Pawluczyk
authors.affiliation: Department of Infection, Immunity and inflammation, University of Leicester, Leicester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pervez
authors.affiliation: Department of Infection, Immunity and inflammation, University of Leicester, Leicester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ghaderi Najafabadi
authors.affiliation: Academic and Children׳s Renal Unit, University of Bristol, Southmead Hospital, Bristol, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Saleem
authors.affiliation: Department of Infection, Immunity and inflammation, University of Leicester, Leicester, UK; John Walls Renal Unit, Leicester General Hospital Leicester, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Topham
mesh_terms: D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology; D050199:Podocytes / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology
chemical_list: D018955:CD36 Antigens; C518288:FITC-albumin; D005227:Fatty Acids; D008565:Membrane Proteins; D009829:Oleic Acids; D012709:Serum Albumin; D013388:Succinimides; C113267:nephrin; C120556:sulfo-N-succinimidyl oleate; C505407:CASP3 protein, human; D053148:Caspase 3; D016650:Fluorescein-5-isothiocyanate
keywords: Albumin; CD36; Fatty acids; Podocytes