Induction of protein kinase Cδ subspecies in neurons and microglia after transient global brain ischemia
Induction of protein kinase Cδ subspecies in neurons and microglia after transient global brain ischemia
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DOI：
10.1097/00004647-200001000-00013
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发表时间：
2000-01-01
影响因子：
6.3
通讯作者：
Koistinaho, J
中科院分区：
文献类型：
--
作者：
Koponen, S;Goldsteins, G;Koistinaho, J
全脑缺血后CA1神经元的延迟死亡与凋亡基因的诱导有关，并受到蛋白质合成抑制剂的抑制，这表明CAI锥体神经元的变性是一个需要新基因表达的活跃过程。短暂性整体缺血模型已被广泛用于识别延迟神经元细胞死亡的酶和其他蛋白质。研究了大鼠四血管闭塞模型造成的全脑缺血 20 分钟后蛋白激酶 C (PKC) 亚种的表达。在研究的多个 PKC 亚种中，只有 PKC δ mRNA 在 CAI 锥体神经元中在缺血后 24 小时以及在激活的小胶质细胞中在缺血后 3 至至少 7 天显着上调。缺血后 8 小时和 3 天的皮质中也发现了 PKC delta mRNA 的诱导。这种皮质而非海马的诱导受到α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/红藻氨酸受体拮抗剂、6-硝基-7-磺胺苯并[f]喹喔啉-2,3-二酮和糖皮质激素的调节。 N-甲基-D-天冬氨酸受体拮抗剂 MK-801 对 PKC δ 亚种的诱导没有影响。首先在 CAI 锥体神经元中选择性且长期诱导 PKC δ mRNA 和蛋白，随后在激活的小胶质细胞中诱导，这表明 PKC δ 同工酶可能参与短暂性全脑缺血后 CA1 神经元延迟死亡的调节。
The delayed death of CA1 neurons after global brain ischemia is associated with induction of apoptosis genes and is inhibited by protein synthesis inhibitors, suggesting that the degeneration of CAI pyramidal neurons is an active process that requires new gene expression. The transient global ischemia model has been extensively used to identify enzymes and other proteins underlying delayed neuronal cell death. The expression of protein kinase C (PKC) subspecies after 20 minutes of global brain ischemia produced by a four-vessel occlusion model in the rat was studied. From the multiple PKC subspecies studied, only PKC delta mRNA was significantly up-regulated in CAI pyramidal neurons at 24 hours and in activated microglia at 3 to at least 7 days after ischemia. The induction of PKC delta mRNA was also found in the cortex at 8 hours and 3 days after ischemia. This cortical but not hippocampal induction was regulated by an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptor antagonist, 6-nitro-7-sulfamobenzo[f]quinoxaline-2,3-dione, and glucocorticoids. An N-methyl-D-aspartate receptor antagonist, MK-801, was without effect on the induction of PKC delta subspecies. The selective and prolonged induction of the PKC delta mRNA and protein first in CAI pyramidal neurons and at a later stage in activated microglia suggests that the PKC delta isozyme may take part in regulation of the delayed death of CA1 neurons after transient global brain ischemia.