Environmental prognostics: an integrated model supporting lysosomal stress responses as predictive biomarkers of animal health status.
Environmental prognostics: an integrated model supporting lysosomal stress responses as predictive biomarkers of animal health status.
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DOI：
10.1016/j.marenvres.2005.10.005
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发表时间：
2006-04
影响因子：
3.3
通讯作者：
M. Moore;J. Allen;A. McVeigh;A. McVeigh
中科院分区：
文献类型：
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作者：
M. Moore;J. Allen;A. McVeigh;A. McVeigh
潜在的预后使用的溶酶体对环境污染物的反应进行了探讨，在有关预测动物健康的海洋贻贝，基于诊断生物标志物数据。已知细胞溶酶体积累许多金属和有机外源性物质，并且在蓝贻贝的肝胰腺消化细胞和卵巢卵母细胞中证明了致癌的多环芳烃3-甲基胆蒽（3-MC）的溶酶体积累。溶酶体膜的完整性或稳定性似乎是真核生物细胞健康的一般指标;在双壳类软体动物中，它与总氧和氮自由基清除能力、蛋白质合成、生长范围和幼虫活力有关;与DNA损伤呈负相关自噬的特征包括细胞凋亡（微核），以及溶酶体肿胀（体积密度），细胞凋亡和脂褐质沉积，这些都是失败或不完全自噬的特征。使用多变量统计实现多个生物标志物数据的整合，然后通过使用溶酶体膜稳定性作为细胞健康的量度映射到“健康状态空间”上。这被认为是一个关键的一步，对推导的解释框架预测污染物对动物健康的影响，并促进了发展的概念机制模型连接溶酶体损伤和自噬功能障碍与损伤细胞，组织和整个动物。该模型还补充了软体动物肝胰腺细胞的基于细胞的生物能量计算模型的创建和使用，该模型模拟溶酶体和细胞对污染物的反应。更具推测性的是，建议使用生物标志物反应和建模的耦合经验测量，作为开发用于预测环境健康的操作工具箱的实用方法。
The potential prognostic use of lysosomal reactions to environmental pollutants is explored in relation to predicting animal health in marine mussels, based on diagnostic biomarker data. Cellular lysosomes are already known to accumulate many metals and organic xenobiotics and the lysosomal accumulation of the carcinogenic polycyclic aromatic hydrocarbon 3-methylcholanthrene (3-MC) is demonstrated here in the hepatopancreatic digestive cells and ovarian oocytes of the blue mussel. Lysosomal membrane integrity or stability appears to be a generic indicator of cellular well-being in eukaryotes; and in bivalve molluscs it is correlated with total oxygen and nitrogen radical scavenging capacity (TOSC), protein synthesis, scope for growth and larval viability; and inversely correlated with DNA damage (micronuclei), as well as lysosomal swelling (volume density), lipidosis and lipofuscinosis, which are all characteristic of failed or incomplete autophagy. Integration of multiple biomarker data is achieved using multivariate statistics and then mapped onto “health status space” by using lysosomal membrane stability as a measure of cellular well-being. This is viewed as a crucial step towards the derivation of explanatory frameworks for prediction of pollutant impact on animal health; and has facilitated the development of a conceptual mechanistic model linking lysosomal damage and autophagic dysfunction with injury to cells, tissues and the whole animal. This model has also complemented the creation and use of a cell-based bioenergetic computational model of molluscan hepatopancreatic cells that simulates lysosomal and cellular reactions to pollutants. More speculatively, the use of coupled empirical measurements of biomarker reactions and modelling is proposed as a practical approach to the development of an operational toolbox for predicting the health of the environment.