Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland.
Mitochondrion. 2012 Jan;12(1):138-43. doi: 10.1016/j.mito.2011.06.002. Epub 2011 Jun 17.
PKC is implicated in the regulation of mitochondrial metabolism. We examined the association of PKCβ with mitochondria and followed postischemic changes in its amount in mitochondria isolated from ischemia-vulnerable (CA1) and ischemia-resistant (CA2-4,DG) hippocampus in gerbil model of transient brain ischemia. Our observations suggest that transient ischemic episode induces a significant, rapid and long lasting increase of PKCβ in mitochondria in CA2-4,DG, which may bespeak neuroprotection. In organotypic hippocampal culture (OHC) model of neurodegeneration, PKCβ inhibition imposed over NMDA toxicity extended the death area beyond the CA1. These results suggest that PKCβ might have a protective effect against excitotoxic damage in rat OHC. The pull-down method and LC-MS/MS analysis revealed mitochondrial proteins that can bind directly with PKCβΙ. The proteins were parts of i) mitochondrial redox carriers forming the electron transport chain including ATP synthase and ii) MPTP: ANT and creatine kinase. PKCβ acting through mitochondrial proteins could play a role in protecting the cells from death by e.g. influencing ROS and ATP production after ischemia in CA2-4,DG region of the hippocampus.
蛋白激酶 C（PKC）参与调节线粒体代谢。我们研究了 PKCβ与线粒体的关联，并观察了短暂性脑缺血沙土鼠模型中海马易损区（CA1）和不易损区（CA2-4、DG）分离出的线粒体中 PKCβ含量的缺血后变化。我们的观察结果表明，短暂性缺血发作诱导 CA2-4、DG 区线粒体中 PKCβ的显著、快速和持久增加，这可能表明具有神经保护作用。在神经退行性变的器官型海马培养（OHC）模型中，PKCβ 抑制剂对 NMDA 毒性的抑制作用将死亡区域扩大到 CA1 以外。这些结果表明，PKCβ 可能对大鼠 OHC 的兴奋性毒性损伤具有保护作用。下拉法和 LC-MS/MS 分析揭示了可与 PKCβΙ直接结合的线粒体蛋白。这些蛋白是 i）形成电子传递链的线粒体氧化还原载体的一部分，包括 ATP 合酶和 ii）MPTP：ANT 和肌酸激酶。PKCβ 通过线粒体蛋白发挥作用，可通过例如影响 CA2-4、DG 区缺血后 ROS 和 ATP 的产生，从而在细胞死亡中发挥保护作用。
