Comparative cellular toxicity of hydrophilic and hydrophobic microcystins on Caco-2 cells.
Comparative cellular toxicity of hydrophilic and hydrophobic microcystins on Caco-2 cells.
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DOI：
10.3390/toxins4111008
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发表时间：
2012-10-25
期刊：
影响因子：
4.2
通讯作者：
Meriluoto JA
中科院分区：
文献类型：
--
作者：
Vesterkvist PS;Misiorek JO;Spoof LE;Toivola DM;Meriluoto JA
微囊藻毒素（MC），蓝藻肽肝毒素，包括超过100种不同的变体。它们是相当极性的分子，但一些变体在分子的高度可变部分含有疏水氨基酸残基。在MC-LF和MC-LW中，疏水性更强的苯丙氨酸(F)和色氨酸(W)分别取代了MC-LR中的精氨酸(R)。根据结构的不同，预计微囊藻毒素具有不同的体内毒性和生物利用度，但只有少数研究考虑了更疏水的变体的毒性。本研究表明，MC-LF和MC-LW对Caco-2细胞的细胞毒作用比MC-LR更明显。MC-LW处理Caco-2细胞，尤其是MC-LF处理Caco-2细胞表现出明显的凋亡特征，包括收缩和起泡，细胞间的粘附丧失。用MC-LF、MC-LW和MC-LR分别观察到细胞增殖和活力的明显降低（以线粒体脱氢酶的活性来评估）。通过乳酸脱氢酶渗漏量测定细胞毒性。与对照组和MC-LR相比，疏水性更强的MC-LW和MC-LF诱导的乳酸脱氢酶渗漏明显增加，表明质膜受到损伤。三种毒素均能抑制蛋白磷酸酶1，MC-LF和MC-LW的抑制程度较MC-LR弱。疏水性越强的微囊藻毒素的毒性潜力越高，这不能用生物物理实验来解释。综上所述，我们的数据表明，越疏水的微囊藻毒素变异对Caco-2细胞的毒性越高。
Microcystins (MC), cyanobacterial peptide hepatotoxins, comprise more than 100 different variants. They are rather polar molecules but some variants contain hydrophobic amino acid residues in the highly variable parts of the molecule. In MC-LF and MC-LW, the more hydrophobic phenylalanine (F) and tryptophan (W), respectively, have replaced arginine (R) in MC-LR. Depending on the structure, microcystins are expected to have different in vivo toxicity and bioavailability, but only a few studies have considered the toxic properties of the more hydrophobic variants. The present study shows that MC-LF and MC-LW have more pronounced cytotoxic effects on Caco-2 cells as compared to those of MC-LR. Treatment of Caco-2 cells with MC-LW and especially MC-LF showed clear apoptotic features including shrinkage and blebbing, and the cell–cell adhesion was lost. An obvious reduction of cell proliferation and viability, assessed as the activity of mitochondrial dehydrogenases, was observed with MC-LF, followed by MC-LW and MC-LR. Cytotoxicity was quantified by measuring lactate dehydrogenase leakage. The more hydrophobic MC-LW and MC-LF induced markedly enhanced lactate dehydrogenase leakage compared to controls and MC-LR, indicating that the plasma membrane was damaged. All of the three toxins examined inhibited protein phosphatase 1, with MC-LF and MC-LW to a weaker extent compared to MC-LR. The higher toxic potential of the more hydrophobic microcystins could not be explained by the biophysical experiments performed. Taken together, our data show that the more hydrophobic microcystin variants induce higher toxicity in Caco-2 cells.
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DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
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作者：
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影响因子：
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发表时间：
1990-12-31
影响因子：
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作者：
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影响因子：
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