Is toxicological pathology characterised by a loss of system complexity?

Moore, Michael N.

doi:10.1016/j.marenvres.2009.11.006

Cited by 18 publications

(29 citation statements)

References 25 publications

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“…However, PCA and cluster analysis does not integrate the various biomarkers in a functionally meaningful way, and is only the first stage in developing numerical and network models for environmental impact on the health of sentinel animals such as mussels and earthworms (Allen and Moore, 2004;Moore, 2010;Sforzini et al, 2015Sforzini et al, , 2017. In order to encapsulate the cellular physiological processes, it is necessary to interconnect the biomarker data into a logical framework.…”

Section: Discussionmentioning

confidence: 99%

“…This was done using a network model of the physiological/pathological processes known to occur in the digestive cells. Complexity is a measure of the interconnectedness of the network and can be used as an indicator of homeostasis (Lewis et al, 1992;Moore, 2010;Moore et al, 2015;Sedivy, 1999). Complexity of the whole system increases when sub-systems, such as detoxication and antioxidant protective processes, augmented autophagy, protein degradation and induction of stress proteins, are up-regulated and start to interact significantly as part of a response to low-level stress (i.e., biphasic or hormetic response; Moore, 2010;Moore et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The generic cell model described by Moore (2010) has been developed from extensive published data in the environmental toxicology and biomedical literature, and the large-scale organisation of metabolic networks (Cuervo, 2004;Di Giulio & Hinton, 2008;Jeong et al, 2000;Klionsky & Emr, 2000). The generic cellular interaction network was constructed around the essential processes of feeding, excretion and energy metabolism.…”

Section: Network Modelling Of Biomarker Data 281 Model Descriptionmentioning

confidence: 99%

“…Mathematical models provide the conceptual and mathematical formalism to integrate molecular, cellular and whole animal processes (Allen & McVeigh, 2004;Allen & Moore, 2004;Moore & Noble, 2004). Previous studies have shown that network complexity (as evaluated using network connectedness -connectance CV%-and node size) can be used as an indicator of homeostasis or health in cellular systems (Moore, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Modelling is essential for the derivation of explanatory frameworks that facilitates the development of a predictive capacity for estimating outcomes or risk associated with particular disease processes and stressful treatments (Moore, 2010;Moore & Noble, 2004;Moore et al, 2015). Previous studies on mussels and earthworms have shown that there is a strong relationship between lysosomal membrane stability (LMS), as an indicator of cellular health, and the responses of numerous stress biomarkers (Moore et al, 2006a;Sforzini et al, 2015Sforzini et al, , 2017.…”

Section: Introductionmentioning

confidence: 99%

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Role of mTOR in autophagic and lysosomal reactions to environmental stressors in molluscs

et al. 2018

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Lysosomal membrane stability (LMS) has been used in various organisms as a very sensitive biomarker of stress. However, despite the abundance of data about regulation of the autophagic process in mammals, in the invertebrates there is only limited mechanistic understanding. Marine mussels (Mytilus galloprovincialis Lam.) are bivalve molluscs, widely used as models in ecotoxicology and as environmental bioindicators of sea water quality. In order to elucidate this fundamental process, in the present study, mussels were exposed for 3 days to a "priority", ubiquitous environmental contaminant, benzo[a]pyrene (B[a]P) at different concentrations (i.e. 5, 50, 100 μg/L seawater). B[a]P accumulated in lysosomes of digestive tubule epithelial cells (digestive cells) and in enlarged lipid-rich lysosomes (autolysosomes) as detected by immunofluorescence and UV-fluorescence. B[a]P also activated the autophagic process with a marked decrease of LMS and concurrent increase in lysosomal/cytoplasmic volume ratio. Dephosphorylation of mTOR contributes to increased lysosomal membrane permeability and induced autophagy. B[a]P induced a decrease in phosphorylated (active form) mTOR. The probable role of mTOR in cell signalling and the regulation of the cellular responses to the contaminants has been also confirmed in a field study, where there was significant inactivation of mTOR in stressed animals. Statistical and network modelling supported the empirical investigations of autophagy and mTOR; and was used to integrate the mechanistic biomarker data with chemical analysis and DNA damage.

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Section: Discussionmentioning

confidence: 99%