AIM To clarify the
signal transduction mechanism of apoptosis induced by AlCl 3 and the mechanism of neurotoxicity of aluminum.
METHODS Cortical neurons were separated and cultured from newborn (less than 24 h) Sprague Dawley(SD) rats. The method of FDA fluorescein staining was used to detect the viability of cortical neurons. Hoechst33258 nucleus staining and agarose gel electrophoresis were used to observe the characters of apoptosis. And SAPK/JNK assay kit was used to measure SAPK/JNK activity. RESULTS AlCl 3 (10-1000 μmol·L -1 ) decreased the viability and induced apoptosis of cortical neurons. The phosphorylation of SAPK/JNK increased
significantly (4.2 times as compared to control, P<0.01), and the activity of SAPK/JNK was elevated when cortical neurons were cultured with 1000 μmol·L -1 AlCl 3 for 6 h. But when the cortical neurons were pretreated with CEP 11004 (1-10 μmol·L -1 ) for 6 h prior to treatment with 1000 μmol·L -1 AlCl 3 for 6 h, the phosphorylation of SAPK/JNK decreased significantly in a dose dependent manner (2.3, 1.2 and 0.9 times as compared to control respectively, P<0.05). It indicated the JNK inhibitor CEP 11004 promoted the survival of cortical neurons by blocking apoptosis and protected the neurons. CONCLUSION CEP 11004 inhibited the activation of SAPK/JNK to protect cortical neurons from apoptosis induced by aluminum chloride.