Glutathione S-transferase pi regulates UV-induced JNK signaling in SH-SY5Y neuroblastoma cells.
Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a key event in apoptosis. The cellular mechanisms underlying the control of JNK catalytic activity before and immediately after stress in neuronal cells are still not completely understood. Under resting conditions the basal activity of JNK is low, since JNK is kept inactive by the presence of one or more endogenous repressors, including glutathione S-transferase pi (GSTpi). The aim of this study was to investigate the control of JNK signaling by GSTpi. We examined the modifications of GSTpi protein expression and oligomerization after UV irradiation-induced stress in human SH-SY5Y neuroblastoma cells. In parallel, we investigated the effect of UV irradiation on JNK activation and c-Jun phosphorylation, and whether apoptosis represents a functional consequence triggered by this signaling pathway. We show that in SH-SY5Y cells JNK phosphorylation and activation precedes c-Jun phosphorylation and caspase-3 cleavage. Importantly, the increase of JNK enzymatic activity correlates with the dissociation of GSTpi-JNK complexes and the increased concentration of GSTpi multimer forms. Results presented herein show for the first time direct interaction between JNK and GSTpi in SH-SY5Y neuroblastoma cells, and suggest that in these cells GSTpi may serve as a regulator of JNK catalytic activity. This work contributes to further elucidate the mechanisms underlying the regulation of JNK activity under stress conditions.
Castro-Caldas
Margarida
M
Research Institute for Medicines and Pharmaceutical Sciences, University of Lisbon, 1649-003 Lisbon, Portugal.
Milagre
Inês
I
Rodrigues
Elsa
E
Gama
Maria João
MJ
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology / Q000528:radiation effects; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000528:radiation effects; D010766:Phosphorylation / Q000528:radiation effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D013312:Stress, Physiological / Q000502:physiology* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000502:physiology / Q000528:radiation effects
D046911:Macromolecular Substances; D016755:Proto-Oncogene Proteins c-jun; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3