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Synergistic effects of toxic elements on heat shock proteins.

Mahmood K, Jadoon S, Mahmood Q, Irshad M, Hussain J - Biomed Res Int (2014)

Bottom Line: The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review.The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors.The adoption of heat shock proteins as "suit of biomarkers in a set of organisms" requires further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Government Post-Graduate College Asghar Mall, Rawalpindi, Pakistan.

ABSTRACT
Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as "suit of biomarkers in a set of organisms" requires further investigation.

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Related in: MedlinePlus

Toxic metals induce HSP70i accumulation in podocytes in a dose-dependent manner. Results of a quantitative western blot analysis of HSP70i accumulation in podocytes treated with various concentrations of individual toxic metals (a) or combinations of two and three toxic metals totaling 10, 20, or 40 mM (b) for 3 days. Values are expressed as ng of HSP70i per mg total protein. Basal HSP70i levels were below the limits of detection [100].
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fig1: Toxic metals induce HSP70i accumulation in podocytes in a dose-dependent manner. Results of a quantitative western blot analysis of HSP70i accumulation in podocytes treated with various concentrations of individual toxic metals (a) or combinations of two and three toxic metals totaling 10, 20, or 40 mM (b) for 3 days. Values are expressed as ng of HSP70i per mg total protein. Basal HSP70i levels were below the limits of detection [100].

Mentions: No data exist regarding the synergistic effects of different toxicants and/or with the other aspects of environmental stresses (temperature, pH, salinity, etc.). For instance, the toxic effect is significantly altered under the additive effects of many heavy metals as compared to cases of isolated single metal toxicity where two or more metals are found in a combination. Individual dose of 20 μM of As, Cd, and Hg induced only a modest HSP70 increase, whereas their combination at the lowest levels of toxicity still induced a greater accumulation of these proteins (Figure 1) [100]. Furthermore, a number of stress genes which respond to heavy metals (such as HSPs and MT) contain metal-response elements (MREs) in their promoter/enhancer region, which is activated by a metal-responsive transcription factor-1 (MTF-1). The response to heat shock is mediated by heat shock transcription factor-1 (HSF-1), which activates a battery of heat shock genes. Synergistic activation has also demonstrated the metal-responsive promoters by heavy metals (Zn or Cd) and heat shock in combination. Heat also stimulates the intracellular accumulation of Zn and Cd when provided exogenously during a heat shock, (in HEK293-mammalian cells) and thus results in a hyperactivation of the metal response pathway. Interestingly, relatively low concentrations of these heavy metals alone hardly induced transcription at all and served as sufficient trigger for such synergistic activation of mammalian HSP70 promoter (Figures 2(a) and 2(b)) [101]. Similarly, water-soluble fractions of different sludge containing varying concentrations of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn), when given separately to human cultured cells (HT29 cell line from gut mucosa), failed to trigger significant expression of HSP72. When given in combination, they exerted a strong synergistic effect by causing significant overexpression of HSP72 (Figure 3) [102]. Increasing concentrations of HSP70 have also been observed in HepG2 cells under the synergistic effects of Cu and Zn as compared with each metal (Figure 4) [80]. Another study conducted by Aït-Aïssa et al. [74] reported that 3,3′,4,4′-tetrachlorobiphenyl (1 mg/kg) strongly induced HSP70, while its coexposure with metals did not modulate significantly its effects. However, 17-beta-oestradiol in combination with Cd/Zn had shown a synergistic effect.


Synergistic effects of toxic elements on heat shock proteins.

Mahmood K, Jadoon S, Mahmood Q, Irshad M, Hussain J - Biomed Res Int (2014)

Toxic metals induce HSP70i accumulation in podocytes in a dose-dependent manner. Results of a quantitative western blot analysis of HSP70i accumulation in podocytes treated with various concentrations of individual toxic metals (a) or combinations of two and three toxic metals totaling 10, 20, or 40 mM (b) for 3 days. Values are expressed as ng of HSP70i per mg total protein. Basal HSP70i levels were below the limits of detection [100].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127286&req=5

fig1: Toxic metals induce HSP70i accumulation in podocytes in a dose-dependent manner. Results of a quantitative western blot analysis of HSP70i accumulation in podocytes treated with various concentrations of individual toxic metals (a) or combinations of two and three toxic metals totaling 10, 20, or 40 mM (b) for 3 days. Values are expressed as ng of HSP70i per mg total protein. Basal HSP70i levels were below the limits of detection [100].
Mentions: No data exist regarding the synergistic effects of different toxicants and/or with the other aspects of environmental stresses (temperature, pH, salinity, etc.). For instance, the toxic effect is significantly altered under the additive effects of many heavy metals as compared to cases of isolated single metal toxicity where two or more metals are found in a combination. Individual dose of 20 μM of As, Cd, and Hg induced only a modest HSP70 increase, whereas their combination at the lowest levels of toxicity still induced a greater accumulation of these proteins (Figure 1) [100]. Furthermore, a number of stress genes which respond to heavy metals (such as HSPs and MT) contain metal-response elements (MREs) in their promoter/enhancer region, which is activated by a metal-responsive transcription factor-1 (MTF-1). The response to heat shock is mediated by heat shock transcription factor-1 (HSF-1), which activates a battery of heat shock genes. Synergistic activation has also demonstrated the metal-responsive promoters by heavy metals (Zn or Cd) and heat shock in combination. Heat also stimulates the intracellular accumulation of Zn and Cd when provided exogenously during a heat shock, (in HEK293-mammalian cells) and thus results in a hyperactivation of the metal response pathway. Interestingly, relatively low concentrations of these heavy metals alone hardly induced transcription at all and served as sufficient trigger for such synergistic activation of mammalian HSP70 promoter (Figures 2(a) and 2(b)) [101]. Similarly, water-soluble fractions of different sludge containing varying concentrations of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn), when given separately to human cultured cells (HT29 cell line from gut mucosa), failed to trigger significant expression of HSP72. When given in combination, they exerted a strong synergistic effect by causing significant overexpression of HSP72 (Figure 3) [102]. Increasing concentrations of HSP70 have also been observed in HepG2 cells under the synergistic effects of Cu and Zn as compared with each metal (Figure 4) [80]. Another study conducted by Aït-Aïssa et al. [74] reported that 3,3′,4,4′-tetrachlorobiphenyl (1 mg/kg) strongly induced HSP70, while its coexposure with metals did not modulate significantly its effects. However, 17-beta-oestradiol in combination with Cd/Zn had shown a synergistic effect.

Bottom Line: The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review.The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors.The adoption of heat shock proteins as "suit of biomarkers in a set of organisms" requires further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Government Post-Graduate College Asghar Mall, Rawalpindi, Pakistan.

ABSTRACT
Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as "suit of biomarkers in a set of organisms" requires further investigation.

Show MeSH
Related in: MedlinePlus