McDermott C M, Nho C W, Howard W, Holton B
Department of Biology and Microbiology, Halsey Science Center, University of Wisconsin Oshkosh, 54901, USA.
Toxicon. 1998 Dec;36(12):1981-96. doi: 10.1016/s0041-0101(98)00128-7.
Cyanobacterial toxins, especially the microcystins (MCYST), are found in eutrophied waters throughout the world. These toxins cause hepatocyte damage by inhibiting protein phosphatases 1 and 2A, resulting in hyperphosphorylation of cytoskeletal proteins. Acute intoxication of animals and humans has been reported following MCYST exposure. Okadaic acid, a marine biotoxin, has a similar mechanism of action to MCYST and has been shown to cause apoptosis, a form of programmed cell death, in a variety of cell types. In this study, primary rat hepatocytes (in suspension and monolayer culture), human fibroblasts, human endothelial cells, human epithelial cells, and rat promyelocytes were observed following treatment with MCYST for morphological and biochemical changes typical of apoptosis. Hepatocytes underwent cell membrane blebbing, cell shrinkage, organelle redistribution, and chromatin condensation as early as 30 min following MCYST application (0.8 microM). Other cell types treated with MCYST (100 microM) also showed these morphological changes, but required a longer period of treatment. DNA fragmentation and "ladder" formation occurred in most cell types exposed to MCYST. These observations demonstrate that MCYST causes apoptosis in a variety of mammalian cells.
蓝藻毒素,尤其是微囊藻毒素(MCYST),在世界各地富营养化的水体中均有发现。这些毒素通过抑制蛋白磷酸酶1和2A导致肝细胞损伤,从而使细胞骨架蛋白发生过度磷酸化。据报道,动物和人类在接触微囊藻毒素后会出现急性中毒症状。冈田酸是一种海洋生物毒素,其作用机制与微囊藻毒素相似,已被证明能在多种细胞类型中引发凋亡,即一种程序性细胞死亡形式。在本研究中,观察了原代大鼠肝细胞(悬浮培养和单层培养)、人成纤维细胞、人内皮细胞、人上皮细胞以及大鼠早幼粒细胞在经微囊藻毒素处理后出现的典型凋亡形态学和生化变化。早在应用微囊藻毒素(0.8微摩尔)后30分钟,肝细胞就出现了细胞膜起泡、细胞皱缩、细胞器重新分布以及染色质凝聚等现象。用微囊藻毒素(100微摩尔)处理的其他细胞类型也表现出这些形态学变化,但需要更长的处理时间。在大多数接触微囊藻毒素的细胞类型中都出现了DNA片段化和“梯状”形成。这些观察结果表明,微囊藻毒素可在多种哺乳动物细胞中引发凋亡。