Role of JNK activation in pancreatic beta-cell death by streptozotocin. 2010

Hwanju Cheon, and Jae Min Cho, and Sunshin Kim, and Seung-Hoon Baek, and Moon-Kyu Lee, and Kwang-Won Kim, and Seong-Woon Yu, and Giovanni Solinas, and Soung Soo Kim, and Myung-Shik Lee
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

c-Jun N-terminal kinase (JNK) is activated by cellular stress and plays critical roles in diverse types of cell death. However, role of JNK in beta-cell injury is obscure. We investigated the role for JNK in streptozotocin (STZ)-induced beta-cell death. STZ induced JNK activation in insulinoma or islet cells. JNK inhibitors attenuated insulinoma or islet cell death by STZ. STZ-induced JNK activation was decreased by PARP inhibitors, suggesting that JNK activation is downstream of PARP-1. Phosphatase inhibitors induced activation of JNK and abrogated the suppression of STZ-induced JNK activation by PARP inhibitors, suggesting that the inhibition of phosphatases is involved in the activation of JNK by STZ. STZ induced production of reactive oxygen species (ROS) as potential inhibitors of phosphatases, which was suppressed by PARP inhibitors. PARP-1 siRNA attenuated insulinoma cell death and JNK activation after STZ treatment, which was reversed by MKP (MAP kinase phosphatase)-1 siRNA. These results suggest that JNK is activated by STZ downstream of PARP-1 through inactivation of phosphatases such as MKP, which plays important roles in STZ-induced beta-cell death.

UI MeSH Term Description Entries
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011065 Poly(ADP-ribose) Polymerases Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE. ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000067856 Poly(ADP-ribose) Polymerase Inhibitors Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES. Inhibitors of Poly(ADP-ribose) Polymerase,PARP Inhibitor,Poly(ADP-Ribose) Polymerase Inhibitor,Poly(ADP-ribosylation) Inhibitor,Inhibitors of Poly(ADP-ribose) Polymerases,PARP Inhibitors,Poly(ADP-ribosylation) Inhibitors,Inhibitor, PARP,Inhibitors, PARP
D000071137 Poly (ADP-Ribose) Polymerase-1 A poly(ADP-ribose) polymerase that contains two ZINC FINGERS in its N-terminal DNA-binding region. It modifies NUCLEAR PROTEINS involved in chromatin architecture and BASE EXCISION REPAIR with POLY ADENOSINE DIPHOSPHATE RIBOSE. NAD+ ADP-ribosyltransferase-1,PARP-1 Protein,PARP1 Protein,Poly (ADP-Ribose) Synthase-1,NAD+ ADP ribosyltransferase 1,PARP 1 Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000903 Antibiotics, Antineoplastic Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D013311 Streptozocin An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. Streptozotocin,2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose,Streptozotocine,Zanosar
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings

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