A neuronal C5a receptor and an associated apoptotic signal transduction pathway
A neuronal C5a receptor and an associated apoptotic signal transduction pathway
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DOI：
10.1111/j.1469-7793.1998.679bs.x
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发表时间：
1998-03-15
影响因子：
5.5
通讯作者：
Okada, H
中科院分区：
文献类型：
--
作者：
Farkas, I;Baranyi, L;Okada, H
1.我们报告的第一个实验证据的神经元C5 a受体（nC 5aR）在人类细胞的神经元起源。逆转录-聚合酶链反应（RT-PCR）检测nC 5aR mRNA在TGW人神经母细胞瘤细胞中的表达.通过流式细胞术（FACS）测量，C5 a诱发细胞内钙水平的瞬时增加的发现支持了功能性C5 aR的表达。为了分析nC 5aR的功能，使用C5 aR的反义肽片段。先前的数据显示，C5 aR片段（称为PR 226的肽）在U-937细胞中具有C5 aR激动剂和拮抗剂作用，这取决于肽的浓度。我们发现，同一肽的多抗原肽（MAP）形式（称为PR 226-MAP）诱导TGW细胞核c-fos免疫反应性迅速升高，并导致DNA片段化，这是细胞凋亡的特征性标志.还检测到细胞凋亡的早期电生理事件特征：在肽施用的1-2分钟内记录间歇性钙电流脉冲。C5 a预处理延迟了这种钙内流的发生。我们还证实了细胞凋亡途径通过百日咳毒素敏感的G蛋白与nC 5aR相关。虽然C5 a及其受体对神经元的功能尚不清楚，但这些结果表明，该信号转导途径的异常激活可导致细胞凋亡，随后导致神经变性。
1. We report the first experimental evidence of a neuronal C5a receptor (nC5aR) in human cells of neuronal origin. Expression of nC5aR mRNA was demonstrated by the reverse transcriptase-polymerase chain reaction (RT-PCR) in TGW human neuroblastoma cells.2. Expression of a functional C5aR was supported by the finding that C5a evoked a transient increase in the intracellular calcium level as measured by flow cytometry (FACS).3. To analyse the function of the nC5aR, an antisense peptide fragment of the C5aR was used. Previous data showed that a C5aR fragment (a peptide termed PR226) has C5aR agonist and antagonist effects in U-937 cells depending on the concentration of the peptide. We found that a multiple antigenic peptide (MAP) form of the same peptide (termed PR226-MAP) induced rapid elevation of nuclear c-fos immunoreactivity and resulted in DNA fragmentation, a characteristic sign of apoptosis, in TGW cells.4. Early electrophysiological events characteristic of apoptosis were also detected: intermittent calcium current pulses were recorded within 1-2 min of peptide administration. C5a pretreatment delayed the onset of this calcium influx.5. We also demonstrated that the apoptotic pathway is linked to nC5aR via pertussis toxin-sensitive G-proteins.6. Although the function of C5a and its receptor on neurons is unknown, these results suggest that an abnormal activation of this signal transduction pathway can result in apoptosis and, subsequently, in neurodegeneration.