Podocyte Expression of Membrane Transporters Involved in Puromycin Aminonucleoside-Mediated Injury

Cristina Zennaro, Maria Pia Rastaldi, Lorella Pascolo, Marco Stebel, Elisa Trevisan, Mary Artero, Claudio Tiribelli, Vittorio Di Maso, Michele Carraro

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere66159
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 20 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Zennaro, C., Rastaldi, M. P., Pascolo, L., Stebel, M., Trevisan, E., Artero, M., Tiribelli, C., Di Maso, V., & Carraro, M. (2013). Podocyte Expression of Membrane Transporters Involved in Puromycin Aminonucleoside-Mediated Injury. PLoS One, 8(6), [e66159]. https://doi.org/10.1371/journal.pone.0066159