The l-isoform but not d-isoforms of a JNK inhibitory peptide protects pancreatic β-cells
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- 作者：Alessia Fornoni ; Lorenzo Cobianchi ; Nahir Y. Sanabria ; Antonello Pileggi ; R. Damaris Molano ; Hirohito Ichii ; Samuel Rosero ; Luca Inverardi ; Camillo Ricordi ; Ricardo L. Pastori
- 关键词：Pancreatic islets ; Cytoprotection ; Inflammation ; MAPK ; JNK inhibition ; Retroinverso peptide ; d-Aminoacids ; Diabetes ; Islets transplantation
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 出版时间：2 March 2007
- 年：2007
- 卷：354
- 期：1
- 页码：227-233
- 全文大小：266 K
文摘
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.