The l-isoform but not d-isoforms of a JNK inhibitory peptide protects pancreatic β-cells

Alessia Fornoni, Lorenzo Cobianchi, Nahir Y. Sanabria, Antonello Pileggi, R. Damaris Molano, Hirohito Ichii, Samuel Rosero, Luca Inverardi, Camillo Ricordi, Ricardo L. Pastori

Research output: Contribution to journalArticlepeer-review

Abstract

The activation of c-jun N-terminal kinase (JNK) in pancreatic islets is associated with impaired function and viability, and JNK inhibitory peptides (JNKIs) are cytoprotective. In particular, l-isoforms of JNKIs were shown to improve islets viability, while the d-retroinverso isoform of JNKI (RI-JNKI), with a higher therapeutic potential due to longer half-life, has not been studied. We compared the cytoprotective properties of L-JNKI and RI-JNKI. Treatment of murine islets with L-JNKI resulted in preservation of islet equivalents and greater percentage of viable β-cells in culture. In contrast, RI-JNKI was not protective. We found that L-JNKI but not RI-JNKI prevents endogenous c-jun phosphorylation in insulinoma cells. Moreover, RI-JNKI induced islet cells necrosis and activates the p-38 kinase. In conclusion, L-JNKI directly affects β-cells and ameliorates islet viability and function, while RI-JNKI has toxic effects, limiting its biological application to islet cell biology.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume354
Issue number1
DOIs
Publication statusPublished - Mar 2 2007

Keywords

  • Cytoprotection
  • d-Aminoacids
  • Diabetes
  • Inflammation
  • Islets transplantation
  • JNK inhibition
  • MAPK
  • Pancreatic islets
  • Retroinverso peptide

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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