Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways.
Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways.
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DOI：
10.1242/bio.20122170
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发表时间：
2012-12-15
期刊：
影响因子：
2.4
通讯作者：
Dorange G
中科院分区：
文献类型：
--
作者：
Hanana H;Talarmin H;Pennec JP;Droguet M;Morel J;Dorange G
冈田酸(OA)是一种主要的腹泻性贝类毒素，是蛋白质磷酸酶1和2 A的有效抑制剂。蛋白磷酸酶抑制后的下游信号转导途径尚不清楚，以往的大多数研究结果往往相互矛盾。本研究旨在通过研究OA细胞毒性的信号转导途径，评价其对心肌细胞的影响，并分析其可能的作用机制。我们发现，在处理24 h后，1 µM的OA可导致肌动蛋白细胞骨架的解体、成纤维细胞的圆形和脱落。此外，对心肌细胞的处理显示，MAPK蛋白的顺序激活依赖于OA浓度。我们认为，p38和JNK激活的持续时间是决定文蛤心肌细胞凋亡的关键因素。相反，ERK的激活可能与细胞存活有关。OA诱导的细胞死亡是由caspase3依赖机制介导的MAPK信号转导通路。在文蛤心肌细胞上，OA对自发性搏动频率和内向L钙电流无明显影响，提示即使是最大剂量的OA也不能抑制PP1。
Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often conflicting. The aim of the present study was to evaluate the effects of OA on heart clam cells and to analyse its possible mechanisms of action by investigating the signal transduction pathways involved in OA cytotoxicity. We showed that OA at 1 µM after 24 h of treatment induces disorganization of the actin cytoskeleton, rounding and detachment of fibroblastic cells. Moreover, treatment of heart cells revealed a sequential activation of MAPK proteins depending on the OA concentration. We suggest that the duration of p38 and JNK activation is a critical factor in determining cell apoptosis in clam cardiomyocytes. In the opposite, ERK activation could be involved in cell survival. The cell death induced by OA is a MAPK modulated pathway, mediated by caspase 3-dependent mechanism. OA was found to induce no significant effect on spontaneous beating rate or inward L-type calcium current in clam cardiomyocytes, suggesting that PP1 was not inhibited even by the highest dose of OA.
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影响因子：
3.2
作者：
Baba, T;Udaka, K;Sato, SB
通讯作者：
Sato, SB
影响因子：
4.8
作者：
Fujita, M;Seta, C;Haneji, T
通讯作者：
Haneji, T
影响因子：
7.2
作者：
Genescà, M;Sola, A;Hotter, G
通讯作者：
Hotter, G
DOI：
10.2741/dawson
发表时间：
1999-10-01
期刊：
Frontiers in Bioscience
影响因子：
--
作者：
Dawson, John F.;Holmes, Charles F. B.
通讯作者：
Holmes, Charles F. B.
影响因子：
3.6
作者：
INOMATA, M;SAIJO, N;TANAKA, Y
通讯作者：
TANAKA, Y