title: 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.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA. afornoni@med.miami.edu
authors.forename: Alessia
authors.initials: A
authors.lastname: Fornoni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cobianchi
authors.forename: Nahir Y
authors.initials: NY
authors.lastname: Sanabria
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
authors.forename: R Damaris
authors.initials: RD
authors.lastname: Molano
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ichii
authors.forename: Samuel
authors.initials: S
authors.lastname: Rosero
authors.forename: Luca
authors.initials: L
authors.lastname: Inverardi
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Pastori
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects*; D007527:Isoenzymes; D007536:Isomerism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms; D013552:Swine
chemical_list: D007527:Isoenzymes; D020033:Protein Isoforms; D048031:JNK Mitogen-Activated Protein Kinases