Botha Nicolette, Gehringer Michelle M, Downing Tim G, van de Venter Maryna, Shephard Enid G
Department of Biochemistry and Microbiology, University of Port Elizabeth, P.O. Box 1600, Port Elizabeth 6000, South Africa.
Toxicon. 2004 Jan;43(1):85-92. doi: 10.1016/j.toxicon.2003.10.025.
The increasing presence of toxic cyanobacteria in drinking and recreational water bodies, and their potential to impact on human and animal health is cause for concern. Recent work suggests that apoptosis plays a major role in the toxic effects induced by microcystin-LR (MCLR) in the gastrointestinal tract; however, the biochemical pathway remains elusive. Exposure of CaCo2, a human colon carcinoma cell line, and MCF-7, a cell line deficient in pro-caspase-3, cells to 50 microM MCLR induced similar reductions in cell viability as measured by MTT and LDH leakage. The role of MCLR induced oxidative stress in the initiation of apoptosis was investigated over a 2-hr period, and it was found that there was an increase in the release of H(2)O(2) in the first 30 min of exposure for both cell lines. Both cell lines exhibited a dose-dependent increase in both micro- and millicalpain after 24 h exposure to MCLR suggesting a role for protease activation in MCLR-induced apoptosis in non-hepatic human derived cell lines.
饮用水体和娱乐水体中有毒蓝藻细菌的日益增多及其对人类和动物健康的潜在影响令人担忧。最近的研究表明，细胞凋亡在微囊藻毒素-LR（MCLR）诱导的胃肠道毒性作用中起主要作用；然而，其生化途径仍不清楚。将人结肠癌细胞系CaCo2和缺乏前半胱天冬酶-3的细胞系MCF-7细胞暴露于50微摩尔的MCLR中，通过MTT和LDH泄漏检测发现，细胞活力出现了类似程度的降低。在2小时的时间段内研究了MCLR诱导的氧化应激在细胞凋亡起始中的作用，发现两种细胞系在暴露的前30分钟内H(2)O(2)的释放量均增加。在暴露于MCLR 24小时后，两种细胞系的微钙蛋白酶和毫微钙蛋白酶均呈剂量依赖性增加，这表明蛋白酶激活在MCLR诱导的非肝源性人源细胞系细胞凋亡中起作用。
