The age-related increase in IL-1 type I receptor in rat hippocampus is coupled with an increase in caspase-3 activation
The age-related increase in IL-1 type I receptor in rat hippocampus is coupled with an increase in caspase-3 activation
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DOI：
10.1046/j.1460-9568.2002.02012.x
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发表时间：
2002-06-01
影响因子：
3.4
通讯作者：
Lynch, MA
中科院分区：
文献类型：
--
作者：
Lynch, AM;Lynch, MA
来自若干研究的证据表明，白细胞介素-1 β（IL-1 β）和IL-1 I型受体的表达在海马体中特别高，并且最近已经表明，IL-1 β的浓度在老年大鼠的海马体中增加。在这里，我们报告说，这种增加与IL-1 I型受体的表达增加和IL-1受体相关激酶的活性增加。提出的证据表明，与年龄相关的丝裂原活化蛋白激酶，Jun N-末端激酶（JNK）和p38的活性增加，伴随着增强的caspase-3活性。对活化的caspase-3与活化的p38（p-p38）的共定位分析表明，p-p38对于caspase-3的活化是必需的;而体外分析表明，IL-1 β诱导的caspase-3活性增加被p38抑制剂SB 203580废除。IL-1 β诱导的caspase-3活性的体外增加也被血管活性肠肽（JNK抑制剂）所消除;然而，活化的JNK（p-JNK）和活化的caspase-3的共定位并没有清楚地将JNK确定为caspase-3的上游活化剂。我们建议，这些变化是在老年海马细胞死亡的指标，并建议他们有助于与年龄相关的减少长时程增强的穿通通路颗粒细胞突触。
Evidence from several studies indicates that expression of interleukin-1beta (IL-1beta) and IL-1 type I receptor is particularly high in hippocampus, and it has recently been shown that the concentration of IL-1beta is increased in the hippocampus of the aged rat. Here we report that this increase is coupled with an increase in expression of IL-1 type I receptor and increased activity of IL-1 receptor-associated kinase. The evidence presented indicates that the age-related increase in activity of the mitogen-activated protein kinases, Jun N-terminal kinase (JNK) and p38, was accompanied by enhanced caspase-3 activity. Analysis of colocalization of activated caspase-3 with activated p38 (p-p38) suggested that p-p38 was necessary for activation of caspase-3; while in vitro analysis indicated that the IL-1beta-induced increase in caspase-3 activity was abrogated by the p38 inhibitor, SB203580. The IL-1beta-induced increase in caspase-3 activity in vitro was also abrogated by vasoactive intestinal peptide, which is a JNK inhibitor; however, colocalization of activated JNK (p-JNK) and activated caspase-3 did not clearly identify JNK as an upstream activator of caspase-3. We propose that these changes are indicative of cell death in aged hippocampus and suggest that they contribute to the age-related decrease in long-term potentiation in perforant path granule cell synapses.