BIOLOGY RESEARCH PAPER

Biology Research paper

Abstract

Chemical analyses of complex environmental samples are time consuming and expensive, and have the drawback that they cannot predict the ultimate bioavailability of a chemical compound. In this respect, acute toxicity tests have long been used to supplement chemical analyses. Realising that mortality is too coarse a measure for toxicity, alternative in vitro test systems have been and are being developed, their main advantage being that they allow observation of meaningful morphological or physiological alterations at the cellular or organ level. A different approach has consisted of looking at the level of interaction of chemicals with the different macromolecules in the cell. When the target molecule is part of the defence, repair or detoxification machinery of the cell, it becomes a direct and specific marker of exposure and effect (Stegeman et al., 1992). Stress proteins meet most, if not all, criteria of this latter group of biomarkers. As with other biomarker responses, stress proteins (also referred to as heat shock proteins or Hsp) share the advantage over analytical methods of measuring the actual effective fraction of pollution that affects an organism by integrating multiple exposure routes over a given time interval and for any given number of pollutants.

Introduction

Stress proteins are a group of proteins, which can be divided in families according to their molecular weight. Four major stress protein families of 90, 70, 60 and 1624 kDa are the most prominent and are frequently referred to as Hsp90, Hsp70, Hsp60 and low molecular weight stress proteins (for reviews see Morimoto et al., 1990; Nover, 1991). Each stress protein family comprises multiple isoforms, each of whose synthesis is independently regulated. In unstressed cells they are involved in the maintenance of protein homeostasis, i.e. protein folding, aggregation and trafficking (chaperoning; e.g. Hershko, 1988; Hightower, 1991; High and Stirling, 1993; Lis and Wu, 1993; Rutherford and Zuker, 1994).

Different stress proteins are distinct from each other in their substrate speciticities and cellular function (e.g. Bienz and Pelham, 1987; Lindquist and Craig, 1988). Often stress proteins work in concert with each other and with enzymes that catalyseconformational changes of proteins (e.g. Flynn et al., 1989; Stamnes et al., 1991; High and Stirling, 1993; Tai et al., 1993). Recently it has emerged that the cellular protein folding machinery plays a pivotal role in regulating signalling pathways and transcriptional control (Rutherford and Zuker, 1994). When subjected to treatments causing protein damage, some of the constitutively expressed stress proteins are up-regulated proportionately to the degree of stress (e.g. Hiranuma et al., 1993; Jungmann et al., 1993; Sato et al., 1993; Uney et al., 1993; Zafarullah et al., 1993). Other isoforms (Hsp72 being the most prominent among them), are believed to be synthesized only when the cell is exposed to adverse conditions (e.g. Mizzen and Welch, 1988; Edwards et al., 1990; Chen et al., 1992; Bauman et al., 1993). Under these adverse conditions, stress proteins are thought to counter proteotoxic effects by preventing the denaturation of proteins and holding them in the ...