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EnglishThe 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.
The L-isoform but not D-isoforms of a JNK inhibitory peptide protects pancreatic B-cells / Fornoni Alessia; Cobianchi Lorenzo; Sanabria Nahir; Pileggi Antonello; Molano Demaris; Ichii Hirohito; Rosero Samuel; Inverardi Luca; Ricordi Camillo; Pastori Ricardo. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 354:1(2007), pp. 227-233.
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| Titolo: | The L-isoform but not D-isoforms of a JNK inhibitory peptide protects pancreatic B-cells |
| Autori: | |
| Data di pubblicazione: | 2007 |
| Rivista: | |
| Citazione: | The L-isoform but not D-isoforms of a JNK inhibitory peptide protects pancreatic B-cells / Fornoni Alessia; Cobianchi Lorenzo; Sanabria Nahir; Pileggi Antonello; Molano Demaris; Ichii Hirohito; Rosero Samuel; Inverardi Luca; Ricordi Camillo; Pastori Ricardo. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 354:1(2007), pp. 227-233. |
| 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. |
| Handle: | http://hdl.handle.net/11571/32737 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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