Yang Li, Omori Kyoko, Suzukawa Junko, Inagaki Chiyoko
Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
Neurosci Lett. 2004 Feb 26;357(1):73-5. doi: 10.1016/j.neulet.2003.12.032.
We previously reported that ammonia induced apoptosis in cultured rat hippocampal neurons with moderate increases in the intracellular calcium concentration and decreases in phospho-BAD levels. Since this suggested the involvement of calcineurin in the apoptosis, the effects of calcineurin inhibitors, 1 microM cyclosporin A and 1 microM FK506, on the ammonia-induced neuronal apoptosis were tested. Both of the inhibitors abolished the neuronal apoptosis assessed by double staining with Hoechst 33258 and anti-neurofilament antibody, and the ammonia-induced decrease in phospho-BAD Ser(155) level. Thus, calcineurin appeared to be involved in the dephosphorylation of BAD at the sites including Ser(155) in ammonia-induced apoptosis.
我们之前报道过，氨可诱导培养的大鼠海马神经元凋亡，同时细胞内钙浓度适度升高，磷酸化BAD水平降低。由于这表明钙调神经磷酸酶参与了凋亡过程，因此测试了钙调神经磷酸酶抑制剂1微摩尔环孢素A和1微摩尔FK506对氨诱导的神经元凋亡的影响。两种抑制剂均消除了通过Hoechst 33258和抗神经丝抗体双重染色评估的神经元凋亡，以及氨诱导的磷酸化BAD Ser(155)水平降低。因此，在氨诱导的凋亡过程中，钙调神经磷酸酶似乎参与了包括Ser(155)位点在内的BAD去磷酸化。
