Aluminum-induced apoptosis in cultured cortical neurons and its effect on SAPK/JNK signal transduction pathway.
Aluminum exposure and apoptotic cell death has been implicated in several neurodegenerative diseases. The mechanisms by which aluminum interacts with the nervous system are only partly understood. In this study, we used cultured cortical neurons to investigate the ability of aluminum to induce the apoptosis of neurons and to explore the role of SAPK/JNK (stress-activated protein kinase or c-jun N-terminal kinase) signal transduction pathway on the apoptosis induced by aluminum. We found that aluminum-induced degeneration of cortical neurons involved the DNA fragmentation characteristic of apoptosis, and staining of aluminum-treated neurons with the DNA-binding fluorochrome Hoechst 33258 revealed the typical apoptotic condensation and fragmentation of chromatin. The rate of apoptosis increased significantly (from 4.9 to 13.1, 21.4, and 59.8%, P<0.01), which was measured by TdT-mediated dUTP nick end labeling. Western blot analysis showed that SAPK/JNK activities of cortical neurons varies when the exposure time of AlCl(3) were different. The phosphorylation levels were 4.2, 3.3, 1.9 and 1.1 times greater compared to control cultures for 6, 12, 24, and 48 h, respectively (P<0.01). Furthermore, a JNK pathway inhibitor, CEP-11004 (KT8138) inhibited the activation of SAPK/JNK to protect cortical neurons from apoptosis induced by aluminum chloride. Our study demonstrates that aluminum can induce the apoptosis of cortical neurons and SAPK/JNK signal transduction pathway may play an important role in the apoptosis.
Fu
Hong-Jun
HJ
Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University (Northern Campus), 74 Zhongshan Road 2, Guangzhou 510080, China.
Hu
Qian-Sheng
QS
Lin
Zhong-Ning
ZN
Ren
Tie-Ling
TL
Song
Hong
H
Cai
Cheng-Keng
CK
Dong
Sheng-Zhang
SZ
D000535:Aluminum / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
C469298:CEP-11004; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D000535:Aluminum; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases