Department of Medicine and Biosystemic Science Kyushu University Faculty of Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Department of Neuroinflammation and Brain Fatigue Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Biochem Biophys Res Commun. 2018 Sep 5;503(2):837-842. doi: 10.1016/j.bbrc.2018.06.084. Epub 2018 Jun 21.
Activation of protein kinase C delta (PKCδ) has been linked to the neuroinflammation but the relationship with the various neurodegenerative diseases including the Alzheimer's disease (AD) was mostly elusive. In the AD brains, the special phospholipids, ethanolamine plasmalogens (Pls), were found to be reduced and our previous study showed that these lipids possess neuroprotective and anti-inflammatory functions. In the present study, we could find that these lipids can significantly attenuate the microglial expression of PKCδ in the neuroinflammation model and in the AD model mice brains. We also show an increase of PKCδ in the human postmortem AD brains. In addition, we also report that scallop derived Pls (sPls) inhibited the p38MAPK and JNK protein expression which are involved in the expressional regulation of PKCδ in the microglial cells. In addition, the lentiviral shRNA-mediated knockdown of PKCδ attenuated the LPS-induced p65 (NF-kB) activation and inflammatory cytokine expression, suggesting that the PKCδ can induce the inflammatory response which can be inhibited by the sPls. Taken together, our recent findings suggest that the sPls can attenuate the increased expression of PKCδ associated with the neuro-inflammation in the murine brain.
蛋白激酶 C 亚型 δ（PKCδ）的激活与神经炎症有关，但它与包括阿尔茨海默病（AD）在内的各种神经退行性疾病的关系大多难以捉摸。在 AD 大脑中，特殊的磷脂乙醇胺磷酯（Pls）被发现减少，我们之前的研究表明这些脂质具有神经保护和抗炎作用。在本研究中，我们可以发现这些脂质可以显著减轻神经炎症模型和 AD 模型小鼠大脑中小胶质细胞中 PKCδ 的表达。我们还发现 AD 患者死后大脑中的 PKCδ 增加。此外，我们还报告说，扇贝衍生的 Pls（sPls）抑制了 p38MAPK 和 JNK 蛋白的表达，这涉及到小胶质细胞中 PKCδ 的表达调控。此外，慢病毒 shRNA 介导的 PKCδ 敲低减弱了 LPS 诱导的 p65（NF-kB）激活和炎症细胞因子表达，表明 PKCδ 可以诱导炎症反应，而 sPls 可以抑制这种反应。总之，我们最近的发现表明，sPls 可以减轻与小鼠大脑中神经炎症相关的 PKCδ 表达增加。
