Axonal degeneration induces distinct patterns of phosphatidylserine and phosphatidylethanolamine externalization.
Axonal degeneration induces distinct patterns of phosphatidylserine and phosphatidylethanolamine externalization.
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DOI：
10.1038/s41420-021-00641-7
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发表时间：
2021-09-17
影响因子：
7
通讯作者：
Levin LA
中科院分区：
文献类型：
--
作者：
Faris H;Almasieh M;Levin LA
轴突变性是多种神经退行性疾病的共同特征，但其各种表现背后的机制尚不完全清楚。我们之前证明轴突变性与磷脂酰丝氨酸（PS）的外化有关，磷脂酰丝氨酸（PS）先于变性的形态学证据，对氧化还原敏感，并且在华勒变性慢（WldS）突变动物中延迟。磷脂酰乙醇胺 (PE) 是细胞膜内叶中的另一种主要膜磷脂，鉴于 PS 发出细胞凋亡、吞噬作用和变性信号，我们假设 PS 和 PE 膜动力学在轴突变性中发挥不同的作用。为了检验这一假设，在出生后的大鼠视网膜神经节细胞中用钙离子载体诱导轴突变性，并使用 PS 和 PE 特异性荧光探针来测量其随时间的外化。在未经处理的细胞中，细胞表面 PS 仅在细胞体中很突出。用钙离子载体升高细胞内钙导致细胞体、轴突和轴突生长锥中 PS 外化水平显着增加。与 PS 不同，细胞表面 PE 广泛分布在未处理的细胞中，在体细胞、轴突和轴突末端的水平相当。暴露于钙离子载体后，细胞体和轴突中的 PE 外化显着增加。细胞内钙浓度升高还导致轴突泡的形成，其中仅含有外化的 PS，但不含有 PE。总之，这些结果表明正常和退化神经元中外化 PS 和 PE 的不同模式，表明这些磷脂在传导神经元损伤中的不同作用。
Axonal degeneration is a common feature of multiple neurodegenerative diseases, yet the mechanisms underlying its various manifestations are incompletely understood. We previously demonstrated that axonal degeneration is associated with externalization of phosphatidylserine (PS), which precedes morphological evidence of degeneration, is redox-sensitive, and is delayed in Wallerian degeneration slow (WldS) mutant animals. Phosphatidylethanolamine (PE) is the other major membrane phospholipid in the inner leaflet of the cell membrane, and given that PS signals apoptosis, phagocytosis, and degeneration, we hypothesized that PS and PE membrane dynamics play distinct roles in axonal degeneration. To test this hypothesis, axonal degeneration was induced with calcium ionophores in postnatal rat retinal ganglion cells, and PS- and PE-specific fluorescent probes used to measure their externalization over time. In untreated cells, cell-surface PS was prominent in the cell body alone. Elevation of intracellular calcium with calcium ionophores resulted in significantly increased levels of PS externalization in the cell body, axon, and axon growth cone. Unlike PS, cell-surface PE was diffusely distributed in untreated cells, with comparable levels across the soma, axons, and axon terminals. After exposure to calcium ionophores, PE externalization significantly increased in the cell body and axon. Elevated intracellular calcium also resulted in the formation of axonal blebs which exclusively contained externalized PS, but not PE. Together, these results indicated distinct patterns of externalized PS and PE in normal and degenerating neurons, suggesting a differential role for these phospholipids in transducing neuronal injury.
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影响因子：
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DOI：
10.1152/ajpheart.1998.274.1.h242
发表时间：
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