Applications and pitfalls of stress-proteins in biomonitoring

Bierkens, Johan

doi:10.1016/s0300-483x(00)00304-8

Cited by 150 publications

(99 citation statements)

References 71 publications

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“…A number of conditions should first be met to make full use of hsp70 gene expression as an accurate toxicity biomarker in wholeanimal testing (8,9). For an ideal hsp70 model system, a basic knowledge of normal hsp70 expression under nonstressed conditions is needed to properly assess the significance of results seen after toxin exposure.…”

mentioning

confidence: 99%

Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line.

Blechinger

Warren

Kuwada

et al. 2002

Environ Health Perspect

146

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The toxic effects of cadmium and other heavy metals have been well established, and many of these and other environmental pollutants are known to be embryotoxic or teratogenic. However, it has proven difficult to identify individual cells that respond to toxicants among the wide range of cell populations in an intact animal, particularly during early development when cells are continually changing their molecular and physiologic characteristics as they differentiate. Here we report the establishment of an in vivo system that uses hsp70 gene activation as a measure of cadmium toxicity in living early larvae of transgenic zebrafish carrying a stably integrated hsp70-enhanced green fluorescent protein (eGFP) reporter gene. We demonstrate that eGFP expression in this strain of fish acts as an accurate and reproducible indicator of cell-specific induction of hsp70 gene expression. Furthermore, the transgene responds in a dose-dependent manner at concentrations similar to those observed for morphologic indicators of early-life-stage toxicity and is sensitive enough to detect cadmium at doses below the median combined adverse effect concentration and the median lethal concentration. The stable nature of this transgenic line should allow for extremely rapid and reproducible toxicologic profiling of embryos and larvae throughout development.

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mentioning

confidence: 99%

Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line.

Blechinger

Warren

Kuwada

et al. 2002

Environ Health Perspect

146

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“…We also demonstrated that both E 2 and BPA increased levels of hsp90α and grp94 (Papaconstantinou et al 2001) at doses lower than those necessary for a significant increase in uterine weight (Papaconstantinou et al 2000). The use of hsps as biomarkers of environmental pertubation shows promise despite some criticisms (Bierkens 2000). Levels of hsps increase in response to cellular injury and protein damage to protect the cell by assisting in the correct folding and processing of proteins (Welch 1987).…”

mentioning

confidence: 77%

Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

Papaconstantinou

Fisher

Umbreit

et al. 2002

Environ Health Perspect

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There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown that bisphenol A (BPA), similarly to 17ss-estradiol (E2), increases levels of uterine heat shock proteins (hsps), mainly hsp90alpha and glucose-regulated protein (grp) 94. In this study we investigated whether increases in uterine hsp levels are a specific response of estrogens or estrogen mimics. We therefore examined the ability of a) E2, diethylstilbestrol (DES), and tamoxifen (TAM); b) the xenoestrogens coumestrol (CM), methoxychlor (MXC), BPA, and dibutyl phthalate (DBP); c) the progestin medroxyprogesterone (MED); d) the glucocorticoid dexamethasone (DEX); and e) phytol (PHY), a precursor to a retinoid X and peroxisome proliferator-activating receptor agonist, to increase uterine weights and alter uterine morphology and hsp levels. We showed that DES, TAM, CM, MXC, and BPA significantly increased uterine weights and uterine hsp90alpha and grp94 levels. Even though the doses of CM, MXC, and BPA used were much higher than the E2 dose, those treatments resulted in lower increases in uterine weight. On the other hand, increases in grp94 levels were equal to those induced by E2 treatment. Treatments with MED, DEX, DBP, or PHY did not significantly alter uterine weight or morphology and had no significant effects on uterine hsp levels. The results of this study suggest that only the estrogens increase uterine hsp90alpha and grp94 levels, and that this hsp effect is a more sensitive uterotrophic response than uterine weight increase.

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“…It acts as the ultimate sink for all pollutants or their oxidation products. With rapid industrialization and development, thousands of new chemical compounds are being introduced every year [30]. Each of them has to be considered as potentially hazardous.…”

Section: Hsp70 In Environmental Monitoringmentioning

confidence: 99%

“…As members of the Hsp70 are often the prominent proteins to be expressed following environmental insults, these stress proteins are, therefore, very useful indicators of cellular aggression, and have been used to monitor the impact of environmental factors on various animal species [42][43][44][45] as well as in in vitro models [28,37,41,46,47]. Hsp70 is the target molecule or molecule under investigation because it simultaneously takes part in defense, repair, or detoxification machinery of the cell and becomes a direct and specific indicator of cellular stress [30,[48][49][50][51]. Being integrators of diverse aspects of protein damage, Hsp70 may provide added value in environmental risk assessment by complementing the already existing tests that measure more specific modes of toxic action.…”

Section: Hsp70 In Environmental Monitoringmentioning

confidence: 99%

“…In Drosophila, mammals, and other model organisms studied, Hsps are broadly classified according to the apparent molecular weight, amino acid sequence homologies, and their functional aspects into five major families: Hsp100 family (100-104 kDa), Hsp90 family (82-90 kDa), Hsp70 family (68-75 kDa), Hsp60 family (58-65 kDa), and the small Hsp family (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). The Hsp70 family is the most highly conserved and largest of all the stress protein families; it has also been most extensively studied [16][17][18][19][20][21][22].…”

mentioning

confidence: 99%

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Heat shock response: hsp70 in environmental monitoring

Mukhopadhyay

Nazir

Saxena

et al. 2003

J Biochem & Molecular Tox

145

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Heat shock proteins (Hsps) are a ubiquitous feature of cells in which these proteins cope with stress-induced denaturation of other proteins. Among the different families of Hsps, the 70 kDa family (hsp70) is the most highly conserved and has been most extensively studied. Apart from their primary role in cellular defense under stress condition, a number of studies in recent years have shown the immense potential of hsp70 in pollution monitoring using even transgenic approach both in vivo and in vitro. This article reviews the recent developments in the widespread application of hsp70 in environmental risk assessment. C

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Applications and pitfalls of stress-proteins in biomonitoring

Cited by 150 publications

References 71 publications

Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line.

Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line.

Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

Heat shock response: hsp70 in environmental monitoring

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