Giner Daniel, López Inmaculada, Neco Patricia, Rossetto Ornella, Montecucco Cesare, Gutiérrez Luis M
Instituto de Neurociencias, Centro Mixto CSIC-Universidad Miguel Hernández, Campus de San Juan, 03550 Alicante, Spain.
Eur J Neurosci. 2007 Apr;25(8):2341-8. doi: 10.1111/j.1460-9568.2007.05497.x.
Neuroendocrine chromaffin cells were used to study the mechanism of the snake phospholipase A2 (PLA2) neurotoxin enhancement of exocytosis. Notexin, beta-bungarotoxin, taipoxin or textilotoxin enhanced the fast release of catecholamines elicited by flash photolysis of cytosolic caged calcium. Such an increase correlates with the capacity of these neurotoxins to cause fragmentation of the F-actin cortical barrier with subsequent accumulation of vesicles in the proximity of the plasma membrane. These PLA2 neurotoxins do not act via protein kinase C activation, which is known to promote F-actin fragmentation. Lithium, RO31-8220 and SB216763, three inhibitors of the glycogen synthase kinase 3, prevent both the alteration of the F-actin peripheral cortex and the enhancement of fast release elicited by these neurotoxins. In addition, glycogen synthase kinase 3 has been detected by immunolocalization in a membranous compartment of the chromaffin cell endoplasmic reticulum (ER). These results suggest that the activation of this enzyme plays a major role in the enhancement of exocytosis of the readily releasable granules caused by PLA2 neurotoxins in neuroendocrine chromaffin cells.
神经内分泌嗜铬细胞被用于研究蛇磷脂酶A2（PLA2）神经毒素增强胞吐作用的机制。诺维毒素、β-银环蛇毒素、太攀蛇毒素或织棉蛇毒素增强了由胞质笼形钙的闪光光解引发的儿茶酚胺快速释放。这种增加与这些神经毒素导致F-肌动蛋白皮质屏障破碎并随后使囊泡在质膜附近积累的能力相关。这些PLA2神经毒素并非通过已知可促进F-肌动蛋白破碎的蛋白激酶C激活来发挥作用。糖原合酶激酶3的三种抑制剂锂、RO31-8220和SB216763可防止F-肌动蛋白外周皮质的改变以及这些神经毒素引发的快速释放增强。此外，通过免疫定位在嗜铬细胞内质网（ER）的膜性区室中检测到了糖原合酶激酶3。这些结果表明，该酶的激活在PLA2神经毒素引起的神经内分泌嗜铬细胞中易释放颗粒胞吐增强中起主要作用。
