Enhancement of the Stress Response by Low Concentrations of Arsenite in Arsenite-Pretreated Reuber H35 Hepatoma Cells

doi:10.1006/taap.1995.1095

Toxicology and Applied Pharmacology

Volume 132, Issue 1, May 1995, Pages 146-155

https://doi.org/10.1006/taap.1995.1095 Get rights and content

Abstract

The present study is aimed at determining whether the induction of heat-shock protein (hsp) synthesis, heat-shock mRNAs, and tolerance development after arsenite application has been sensitized to low concentrations of arsenite in Reuber H35 rat hepatoma cells. Using a step-down arsenite treatment, consisting of a 1-hr pretreatment with 100 or 300 μM followed by an incubation with a lower concentration (1-10 μM), H35 cells were shown to exhibit increased sensitivity to low concentrations of sodium arsenite shortly after exposure to the high arsenite concentration, but not any longer when the low concentration was applied 4 hr after pretreatment. In this paper it is shown that exposure of H35 cells to sodium arsenite concentrations of 100 or 300 μM for 1 hr rapidly changes the sensitivity toward a second arsenite treatment with respect to the induction of the heat-shock response. It was observed that under conditions of enhanced sensitivity, an additional increase occurred in hsp synthesis as well as in hsp mRNA (as exemplified by hsp68 mRNA behavior) when low concentrations of arsenite were applied to arsenite pretreated cells. Since no effect of these low concentrations was observed in nonpretreated cells, the effect of step-down treatment results in a higher effect than could be expected based on summation. Furthermore, in sensitized cultures, cells are able to develop a higher level of tolerance in the presence of low concentrations of arsenite. It can be concluded that during a transient period of enhanced sensitivity, low concentrations of the original stressor are able to enhance hsp synthesis and to induce a higher level of tolerance in comparison with control cultures that are sensitized but not incubated in the presence of low concentrations of the original stressor.

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Studying the activation of the heat shock factor (HSF), being the main transcription factor responsible for the expression of HS genes and production of hsp mRNA. Ovelgönne et al.25 were able to show that the low dose stress applied following the higher dose indeed exerted this stimulatory action. Fever-like hyperthermic conditions lead to a prolonged presence of an activated form of HSF as well as an enhanced level of hsp mRNA in cells that were previously heat shocked, which explains the prolonged induction and synthesis of hsps shown in Figure 2.25
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The elevated expression of stress proteins is considered to be a universal response to adverse conditions, representing a potential mechanism of cellular defense against disease and a potential target for novel therapeutics. Exposure to arsenicals either in vitro or in vivo in a variety of model systems has been shown to cause the induction of a number of the major stress protein families such as heat shock proteins (Hsp). Among them are members with low molecular weight, such as metallotionein and ubiquitin, as well as ones with masses of 27, 32, 60, 70, 90, and 110 kDa. In most of the cases, the induction of stress proteins depends on the capacity of the arsenical to reach the target, its valence, and the type of exposure, arsenite being the biggest inducer of most Hsp in several organs and systems. Hsp induction is a rapid dose-dependent response (1–8 h) to the acute exposure to arsenite. Thus, the stress response appears to be useful to monitor the sublethal toxicity resulting from a single exposure to arsenite. The present paper offers a critical review of the capacity of arsenicals to modulate the expression and/or accumulation of stress proteins. The physiological consequences of the arsenic-induced stress and its usefulness in monitoring effects resulting from arsenic exposure in humans and other organisms are discussed.
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Regular ArticleEnhancement of the Stress Response by Low Concentrations of Arsenite in Arsenite-Pretreated Reuber H35 Hepatoma Cells

Abstract

Regular Article
Enhancement of the Stress Response by Low Concentrations of Arsenite in Arsenite-Pretreated Reuber H35 Hepatoma Cells