首页> 外文期刊>American Journal of Physiology >Prion protein fragment 106-126 potentiates catecholamine secretion from PC-12 cells.
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Prion protein fragment 106-126 potentiates catecholamine secretion from PC-12 cells.

机译:on病毒蛋白片段106-126增强了PC-12细胞分泌的儿茶酚胺。

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摘要

The toxic actions of scrapie prion protein (PrP(sc)) are poorly understood. We investigated the ability of the toxic PrP(sc) fragment 106-126 to interfere with evoked catecholamine secretion from PC-12 cells. Prion protein fragment 106-126 (PrP106-126) caused a time- and concentration-dependent augmentation of exocytosis due to the emergence of a Ca(2+) influx pathway resistant to Cd(2+) but sensitive to other inorganic cations. In control cells, secretion was dependent on Ca(2+) influx through L- and N-type Ca(2+) channels, but after exposure to PrP106-126, secretion was unaffected by N-type channel blockade. Instead, selective L-type channel blockade was as effective as Cd(2+) in suppressing secretion. Patch-clamp recordings revealed no change in total Ca(2+) current density in PrP106-126-treated cells or in the contribution to total current of L-type channels, but a small Cd(2+)-resistant current was found only in PrP106-126-treated cells. Thus PrP106-126 augments secretion by inducing a Cd(2+)-resistant Ca(2+) influx pathway and alters coupling of native Ca(2+) channels to exocytosis. These effects are likely contributory factors in the toxic cellular actions of PrP(sc).
机译:对瘙痒病ion病毒蛋白(PrP(sc))的毒性作用了解甚少。我们调查了有毒的PrP(sc)片段106-126干扰PC-12细胞诱发的儿茶酚胺分泌的能力。 on病毒蛋白片段106-126(PrP106-126)由于对Cd(2+)具有抗性但对其他无机阳离子敏感的Ca(2+)流入途径的出现而引起了胞吐作用的时间和浓度依赖性增强。在控制细胞中,分泌取决于通过L型和N型Ca(2+)通道的Ca(2+)流入,但是在暴露于PrP106-126之后,分泌不受N型通道阻滞的影响。而是,选择性L型通道封锁在抑制分泌方面与Cd(2+)一样有效。膜片钳记录显示,在PrP106-126处理的细胞中,总Ca(2+)电流密度没有变化,或者对L型通道的总电流的贡献没有变化,但是仅发现了一个小的Cd(2+)耐受电流。在PrP106-126处理的细胞中。因此,PrP106-126通过诱导Cd(2+)耐药的Ca(2+)流入途径来增加分泌,并改变天然Ca(2+)通道与胞吐作用的耦合。这些影响可能是PrP(sc)毒性细胞作用的促成因素。

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