Stress proteins toxicity

FA Witzmann, CD Fultz, JC Lipscomb. Toxicant-induced alterations in two-dimensional electrophoretic patterns of hepatic and renal stress proteins. Electrophoresis 17 198-202, 1996. 

Temperature is one of the most important variables that determines the distribution and abundance of species (Cossins and Bowler 1987) and imposes critical limits on fitness. As a result of increasing metabolic rate, increasing temperature can increase the uptake and toxicity of contaminants by poikilothermic species, but may also increase rates of detoxification and excretion of toxicants (e.g., pyrethroid insecticides National Research Council of Canada [NRCC] 1987). Temperature extremes in themselves are stressful to organisms, causing induction of various stress proteins, which may be associated with fitness costs (Hoffmann et al. 2003). 

When organisms are confronted with sudden changes such as exposure to potentially toxic substances (heavy metal ions) or the onset of starvation, these stimulations induce the production of the so-called stress responsive proteins. The most thoroughly studied stress proteins include the heat-shock proteins (HSP), the induction of which is a highly conserved response across genera. 

Alcohol toxicity has not been the primary focus of investigations using zebrafish. Instead, zebrafish have been treated with very high doses of alcohol in order to perturb a particular developmental and/or signaling pathway of interest. Exposure of zebrafish embryos to alcohol causes cyclopia, craniofacial abnormalities, and alters gene expression in the ventral aspects of the fore- and mid-brain . Alcohol exposure of zebrafish embryos also induces stress proteins , developmental... 

Ryan, J.A. and L.E. Hightower. Evaluation of heavy-metal ion toxicity in fish cells using a combined stress protein and cytotoxicity assay. Environ. Toxicol. Chem. 13 1231-1240, 1994. 

Remark Werner et al. (2003) found that the sensitivity of fish embryos to toxic chemicals in the San Francisco Bay area is age-dependent. Very young embryos do not manufacture sufficient stress proteins to correct environmentally damaged proteins. Thus, susceptibility to environmental stress in early development is critical to survival of these species. 

Oligodendrocyte progenitors were more vulnerable to Cd toxicity mediated by reactive oxygen species than were mature ohgodendrocytes (Alma-ZAN etal. 2000). Pre-treatment with N-acetyl-cysteine, a thiocompound with antioxidant activity and precursor of glutathione, prevented Cd -induced reduction in glutathione levels and induction of 72 kDa stress protein and diminished Cd uptake and Cd -evoked ceU death. 

The proximal mechanism for induction of stress protein synthesis leading to the activation of HSF and gene activation is not completely understood, but evidence for several possibilities exists. Activation of HSF by prooxidants does not result in the accumulation of specific stress proteins (Bruce et al. 1993). These results suggest that induction of stress proteins by specific metals, whose toxicity is mediated via oxidative damage to membranes or DNA, may be fundamentally different from that of the heat-induced activation of the stress response (Keyse and Tyrrell 1987 Bruce et al. 1993). Thus, metals such as cadmium, mercury, nickel, arsenite, copper, lead, and iron, which induce oxygen free radicals or promote formation of lipid peroxides (Stacey and Klaassen 1981 Halliwell and Gutteridge 1984 Christie and Costa 1984 Kasprzak 1991 Donati et al. 1991), may... 

Prior induction of stress proteins by heat or metals has been shown to protect cells or organisms against toxic injury by metals, such as arsenite or cadmium, as was discussed in more detail in Sect. D. The mechanism for this tolerance is believed to occur via protein-protein interactions, which involves the salvaging of damaged proteins or targeting damaged proteins for proteolysis. 

Strong experimental evidence exists which demonstrates that both MTs and stress proteins play a role in tolerance to toxic metal insults, albeit by different mechanisms. Perhaps both MTs and stress proteins are operating in concert or sequentially, along with other cellular defense mechanisms, e.g., GSH, in a multitiered system to protect cells from toxic injury. 

G. Stress Proteins as Biomarkers of Metal Exposure and Toxicity... 

Goering PL, Fisher BR, Kish CL (1993a) Stress protein synthesis induced in rat liver by cadmium precedes hepatotoxicity. Toxicol Appl Pharmacol 122 139-148 Goering PL, Fisher BR, Kimmel CA, Kimmel GL (1993b) Stress proteins as biomarkers of toxicity. In Travis CC (ed) Use of biomarkers in assessing health and environmental impacts of chemical pollutants. Plenum, New York, pp 95-99... 

Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219 1-14 Hamer DH (1986) Metallothionein. Annu Rev Biochem 55 913-951 Hamet P (1992) Abnormal hsp70 gene expression its potential key role in metabolic defects in hypertension. Clin Exp Pharmacol Physiol [Suppl] 20 53-59 Hansen DK, Anson JF, Hinson WG, Pipkin JL Jr (1988) Phenytoin-induced stress protein synthesis in mouse embryonic tissue. Proc Soc Exp Biol Med 189 136-140... 

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