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

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 beta-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 beta-cells and ameliorates islet viability and function, while RI-JNKI has toxic effects, limiting its biological application to islet cell biology.

authors

Fornoni A,Cobianchi L,Sanabria NY,Pileggi A,Molano RD,Ichii H,Rosero S,Inverardi L,Ricordi C,Pastori RL

doi

10.1016/j.bbrc.2006.12.186

subject

Has Abstract

pub_date

2007-03-02 00:00:00

pages

227-33

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)02865-8

journal_volume

354

pub_type

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