Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro
Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro
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DOI：
10.1038/s41598-020-60781-1
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发表时间：
2020-02-28
影响因子：
4.6
通讯作者：
Matsuda，Yoshikazu
中科院分区：
文献类型：
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作者：
Tsukahara，Tamotsu;Haniu，Hisao;Matsuda，Yoshikazu
认知障碍如痴呆症在晚年很常见，并已被认为是通过一系列机制发生的，包括氧化应激，细胞代谢的年龄相关变化，以及神经元膜磷脂（PL）的损失。PL是一类形成质膜脂质双层的两亲性脂质，并且以高浓度存在于神经元膜中。我们以前的研究表明，通过蛋白酶处理产生的猪肝分解产物（PLDP）可以通过作为PL和溶血磷脂（LPL）的丰富来源来改善老年人的认知功能;然而，其具体组成仍不清楚。因此，本研究使用了一种新的液相色谱电喷雾串联质谱（LC-MS/MS）协议，以确定PLDP中的主要PLs和LPLs。此外，它还评估了鉴定的LPL对体外小胶质细胞活化的影响，包括细胞形状，增殖和细胞形态。所进行的分析的结果表明，PLDP和PLDP衍生的LPL浓度依赖性地调节小胶质细胞的激活在体外。特别是，溶血磷脂酰胆碱（LPC）浓度依赖性地促进细胞形态，可能是通过酶自分泌运动因子（ATX）介导的作用，因为抑制ATX也促进细胞形态，而相反，增加ATX产生（通过高水平的LPC处理）消除了这种作用。这些发现表明LPC可能具有神经保护作用，因此支持进一步研究的重要性，以评估其作为治疗靶点治疗年龄相关的认知障碍，包括痴呆症。
Cognitive impairments such as dementia are common in later life, and have been suggested to occur via a range of mechanisms, including oxidative stress, age-related changes to cellular metabolism, and a loss of phospholipids (PLs) from neuronal membranes. PLs are a class of amphipathic lipids that form plasma membrane lipid bilayers, and that occur at high concentrations in neuronal membranes. Our previous study suggested that a porcine liver decomposition product (PLDP) produced via protease treatment may improve cognitive function at older ages, by acting as a rich source of PLs and lysophospholipids (LPLs); however, its specific composition remains unclear. Thus, the present study used a novel liquid chromatography electrospray ionization tandem mass spectrometric (LC-MS/MS) protocol to identify the major PLs and LPLs in PLDP. Furthermore, it assessed the effect of identified LPLs on microglial activationin vitro, including cell shape, proliferation, and cell morphology. The results of the conducted analyses showed that PLDP and PLDP-derived LPLs concentration-dependently modulate microglial activationin vitro. In particular, lysophosphatidylcholine (LPC) concentration-dependently promotes cell morphology, likely via effects mediated by the enzyme autotaxin (ATX), since inhibiting ATX also promoted cell morphology, while conversely, increasing ATX production (via treatment with high levels of LPC) abolished this effect. These findings suggest that LPC is likely neuroprotective, and thus, support the importance of further research to assess its use as a therapeutic target to treat age-related cognitive impairments, including dementia.