Research for stress signalling underlying neuro-degenerating disease

在海马神经元中观察到凋亡的加速和半胱天冬酶的激活。在这里，我们研究了海马钙蛋白和海马钙蛋白与混合谱系激酶（MLK）3之间的关系，MLK 3是已知导致神经元凋亡的。MLK 3以钙依赖的方式进行免疫共沉淀。免疫复合物激酶测定显示，MLK 3激酶活性在海马CA 1钙蛋白缺陷小鼠高于野生型小鼠。体外激酶活性测定结果表明，重组人钙调素对MLK 3激酶活性具有钙依赖性抑制作用。海人酸诱导的神经元凋亡在MLK 3活性增强的同时，在β-calcin缺陷小鼠中加速。这些结果表明，海马钙蛋白通过直接相互作用抑制MLK 3激酶活性，并下调海马神经元的凋亡信号。

Acceleration of apoptosis and activation of caspases are observed in hippocalcin deficient hippocampal neurons. Here we examined the relation between hippocalcin and Hippocalcin and mixed lineage kinase (MLK)3, which is known to lead neuronal apoptosis.MLK3 were co-immunoprecipitated in a calcium-dependent manner. Immunocomplex kinase assay revealed that MLK3 kinase activity in hippocalcin deficient hippocampus was higher than that in wild type mice. In vitro kinase assay showed that recombinant hippocalcin inhibited MLK3 kinase activity in a calcium-dependent manner. Kainic acid-induced neuronal apoptosis was accelerated in hippocalcin deficient mice accompanied with enhancement in MLK3 activity. These results indicate that hippocalcin inhibits MLK3 kinase activity via direct interaction, and down-regulates apoptosis signaling in hippocampal neurons.