The l-isoform but not d-isoforms of a JNK inhibitory peptide protects pancreatic beta-cells |
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Authors: | Fornoni Alessia Cobianchi Lorenzo Sanabria Nahir Y Pileggi Antonello Molano R Damaris Ichii Hirohito Rosero Samuel Inverardi Luca Ricordi Camillo Pastori Ricardo L |
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Institution: | Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA. afornoni@med.miami.edu |
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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. |
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Keywords: | Pancreatic islets Cytoprotection Inflammation MAPK JNK inhibition Retroinverso peptide d-Aminoacids" target="_blank">d-Aminoacids Diabetes Islets transplantation |
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