Cellular Responses to Stress

Abstract

Since the evolution of the cellular phenotype, prokaryotic and eukaryotic cells have had to cope with adverse changes in their environment. Although cells have evolved many distinct stress responses, this chapter will focus on three major, highly conserved, response systems, i.e., the genotoxic response system, which is activated by DNA damage; the oxidative stress response system, which is activated by excess reactive oxygen species (ROS) and imbalances in the oxidant/antioxidant status within cells; and the heat shock response, which is activated by exposure to heat and other agents that adversely affect protein folding (Fig. 1). The sections dealing with each of the stress response systems begin with a description of the prokaryotic stress response because, in most instances, the prokaryotic systems are the best understood. This is followed by a discussion of the eukaryotic stress response systems, focusing on yeast and mammals. Finally, each section concludes with a discussion about what is known concerning the induction of these stress response systems in mammalian embryos, particularly postimplantation mammalian embryos. Normal embryonic development requires a precisely orchestrated chain of temporal and spatial events, and any alterations in this chain could lead to altered development and subsequent pathogenesis. Although the mammalian embryo develops within the protective environment of the uterus, this protection is not absolute and we now know that mammalian development can be perturbed by a wide variety of chemical and physical agents, many of which are known to induce one or more of these stress systems in nonembryonic systems. Thus understanding the embryo’s stress response capabilities is essential to the understanding of how developmental toxicants exert their toxicity.