A genetic defect in complex I of the mitochondrial electron transport chain (ETC) is implicated in the etiology of Parkinson's disease (PD), and has been studied in cybrid mitochondrial transgene cells based on the SH-SY5Y neuroblastoma. We sought to characterize further the mechanisms and time cour
UV-induced apoptosis in SH-SY5Y cells: Contribution to apoptosis by JNK signaling and cytochrome c
✍ Scribed by C. Mikaela D. Berglund; Ann-Cathrin Radesäter; Mats A.A. Persson; Samantha L. Budd Haeberlein
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 386 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Activation of the c‐Jun N‐terminal kinase (JNK) pathway is suggested to be required for neuronal apoptosis. We investigated the role of JNK on phosphorylation of c‐Jun, Bcl‐2, and apoptotic translocation of cytochrome c (cyt c) in UV‐induced apoptosis in human neuroblastoma SH‐SY5Y cells. We confirm that UV irradiation induces both apoptosis and necrosis in SH‐SY5Y cells and that phosphorylation of JNK at Thr183/Tyr185 in SH‐SY5Y cells treated with UV is an early event preceding apoptosis. We also demonstrate that phosphorylation of c‐Jun at Ser63 is an early event coinciding with JNK activation, and that the phosphorylation of c‐Jun is partially prevented by the JNK inhibitor SP600125. Despite the use of SP600125, the amount of cyt c released into the cytoplasm is not diminished and SP600125 is also unable to decrease the extent of UV‐induced apoptosis. These data support the hypothesis that in this system, UV‐induced apoptosis is not dependent exclusively on JNK activation. Possible involvement of cyclin‐dependent kinases (CDKs) in c‐Jun phosphorylation at Ser63 was excluded by pretreating UV‐irradiated SH‐SY5Y cells with the CDK1/2/5 inhibitor roscovitine. © 2004 Wiley‐Liss, Inc.
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