title: Podocyte expression of membrane transporters involved in puromycin aminonucleoside-mediated injury.
abstract: Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small molecule transporter families have been found in the podocyte membrane, but expression and function of membrane transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA). We observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA, suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion Transporter Polypeptides (OATP/Oatp) family of influx transporters, and P-glycoprotein, a member of the MultiDrug Resistance (MDR) efflux transporter family. Expression of OATP/Oatp transporters was modified by PA treatment. Similarly, in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the engagement of the molecule upon PA administration. In summary, we have characterized some of the small molecule transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte homeostasis and in the pathogenesis of podocyte injury.
authors.affiliation: Department of Medical, Surgery and Health Sciences, Università degli Studi di Trieste, Trieste, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
authors.forename: Lorella
authors.initials: L
authors.lastname: Pascolo
authors.forename: Marco
authors.initials: M
authors.lastname: Stebel
authors.forename: Elisa
authors.initials: E
authors.lastname: Trevisan
authors.forename: Mary
authors.initials: M
authors.lastname: Artero
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiribelli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Di Maso
authors.forename: Michele
authors.initials: M
authors.lastname: Carraro
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000633:toxicity; D001692:Biological Transport / Q000187:drug effects; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D019610:Cytoprotection; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects; D008297:Male; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010400:Penicillin G / Q000378:metabolism / Q000494:pharmacology; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D027361:Organic Anion Transporters; D012709:Serum Albumin; D011692:Puromycin Aminonucleoside; D016572:Cyclosporine; D010400:Penicillin G