Linking Lysosomal Biomarkers and Ecotoxicological Effects at Higher Biological Levels - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 111

2002, 2004; Moore et al. 1978, 1979, 1984, 1985, 1986, 1987, 1996, 2006a, b, c; Moore and Clarke
1982; Axiak et al. 1988; Cajaraville et al. 1995a, b; Da Ros et al. 2000; Marigómez and Baybay-
Villacorta 2003; Marigómez et al. 2005a, b). Autophagy, which is the degradation of cel-
lular components in lysosomes, is implicated in many disease processes, cell death, and
adaptive responses (Cuervo 2004). Regulation of this highly conserved group of cellular
processes appears to be very similar in eukaryotic organisms ranging from yeasts to man
(Klionsky and Emr 2000; Cuervo 2004; Levine 2005).
Other related lysosomal perturbations can also occur such as lysosomal swelling, accu-
mulation of lipid (lipidosis), and age pigment or lipofuscin (lipofuscinosis)—all of these
changes have been described in molluscan digestive gland cells (Moore 1976, 1988; Moore
et al. 1978, 1979, 2006a; Lowe et al. 1981; Nott and Moore 1987; Krishnakumar et al. 1990,
1994; Regoli 1992; Cajaraville et al. 1995a, b, 2000; Etxeberria et al. 1995; Marigómez at al.
1996, 2005a, b; Domouhtsidou and Dimitriadis 2001; Marigómez and Baybay-Villacorta
2003; Kalpaxis et al. 2004).
There is a substantial body of literature documenting the harmful effects of cop-
per and PAHs on both blue ( Mytilus spp.) and green ( Perna spp.) mussels; much of
this involves responses of the lysosomal-vacuolar system in the cells of the digestive
gland (Viarengo 1989; Krishnakumar et al. 1990, 1994; Moore 1990; Viarengo and Nott
1993). Autophagy of cellular components is associated with the lysosomal reactions
and includes autophagic sequestration of copper-induced metallothionein (Viarengo
and Nott 1993; Viarengo et al. 1985), microautophagy induced by phenanthrene, and
phospholipidosis induced by anthracene and phenanthrene (Lüllmann-Rauch 1979;
Nott and Moore 1987).
In eukaryotic cells, the first tier of defense against oxidative damage is provided by
xenobiotic transporters, biotransformation enzymes, and antioxidant protection enzymes,
such as superoxide dismutase and catalase (Livingstone 2001; Moore 2004; Chapter 3).
Lysosomal autophagy provides a second line of defense, by removing oxidatively damaged
proteins and impaired organelles and even portions of the nucleus and DNA (Bergamini et
al. 2003; Cuervo 2004). Consequently, when the first line of defensive systems is overcome,
autophagy protects the cell against the harmful effects of damaged and malfunctioning
proteins, which can form aggregates that will accumulate irreversibly in cells (Grune et al.
2004; Kiffen et al. 2004; Moore 2004; Moore et al. 2006a, b, c). Autophagy may also serve as
a third tier of defense: when autophagic capabilities are compromised, the autophagic sys-
tem can trigger programmed cell death (Lockshin and Zakeri 2004) to remove irreversibly
damaged cells and thereby maintain organ integrity.
5.2.2 Development and Use of Lysosomal Biomarkers in
Assessing Effects of Environmental Stressors
Understandably, the concerns of environmental managers and regulators are largely
focused on the ecosystem level and not individual animals (Xu et al. 2002; Rice 2003).
Unfortunately, the necessary epidemiological (actually epizootiological ) data for pollutant
impact on sentinel animals that should permit a more comprehensive understanding of
possible causal links between animal and ecosystem health are often limited or fragmen-
tary, both spatially and temporally (Xu et al. 2002; Rice 2003). Consequently, alternative
interdisciplinary approaches will be required to identify such links, and we are propos-
ing that the health status of representative sentinel species (e.g., blue and green mussels,
oysters, clams, periwinkles, crabs, flatfish) be used in evaluating health of the environment
(Depledge et al. 1993; Depledge 1994, 1999; Allen and Moore 2004).