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The Stress Response and Stress Proteins
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Martin E. Feder, Dawn A. Parsell, Susan L. Lindquist
A key element in this regulatory system is the HSF (heat shock factor) family of transcription factors. In unstressed cells of most eukaryotes, HSF exists as a monomer in the cytoplasm. Upon stress, HSF trimerizes, migrates to the nucleus, and binds to consensus sequences (HSEs, or heat shock elements) in the promoters of the heat-shock genes, thereby relieving the block to transcription. HSEs occur in the promoters of heat-shock genes, including those for hsp70. However, hsp70 is exceptional in that it, either by itself or in combination with other factors, may inhibit HSF-activated transcription in at least two ways: First, it may interact with unbound HSF to inhibit or reverse trimerization. Second, it may interact with HSF trimers bound to HSE, either promoting their dissociation from HSE or otherwise inhibiting their activation of transcription. In any event, hsp70 is a protein that apparently interacts with its own transcription factor to inhibit its own synthesis (and, in so doing, coordinately regulates the expression of other stress proteins). Unfolded proteins apparently compete with HSF monomer for interaction with hsp70. Thus, as unfolded proteins bind hsp70 and thereby derepress HSF activation of transcription, they set the stage for their own rescue or demise. DnaK, the hsp70 homologue of E. coli, plays a similar role in the autoregulation of the stress response in this organism. Several publications provide more detailed entree to this topic.32,33
Tyrosine Kinase Inhibitors: Targets Other Than FLT3, BCR-ABL, and c-KIT
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Suzanne R. Hayman, Judith E. Karp
A cell’s response to injury or environmental stresses such as heat, inflammation, chemotherapy, or the generation of reactive oxygen species (ROS) may result in cell death, either by apoptosis or necrosis. However, if the level of stress is relatively low, the cell may attempt to survive through the initiation of the heat shock or stress response. This is manifested by the suppression of most new protein synthesis, except for the upregulation of gene expression of Hsps. There are six major families of Hsps grouped according to their approximate weights in kDa (Hsp100, Hsp90, Hsp70, Hsp60, Hsp40, and small Hsps 10–28 kDa). Hsps and their homologs may be found in multiple intracellular compartments including the nucleus, cytosol, mitochondria, and endoplasmic reticulum. Most Hsps are both constitutively expressed and inducible, with increased gene expression resulting from the binding of heat shock transcription factors, particularly heat shock factor (HSF)-1, to heat shock elements located variably upstream from transcription initiation sites. The stress stimulus responsible for this transcriptional activation is thought to be direct protein damage, including oxidative damage by ROS (1).
Changes in Gene Expression During Aging of Mammals
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
Since the hsp-70 gene is expressed after exposure to stresses other than temperature, its expression after subjecting rats to mobility restraint stress has also been studied.38 Rats were restricted from mobility for 30 min to 6 h, RNA was purified from various tissues, and expression of hsp-70 mRNA was assayed by northern blot hybridization. Its expression was greatly enhanced in the adrenal and pituitary, but no significant differences were seen in the brain, muscle, liver, heart, kidney, spleen, and thymus. Hypophysectomy suppressed its expression after stress. Administration of ACTH induced its expression in the adrenal. So ACTH is a physiologic regulator of the expression of hsp-70 in the adrenal. Restraint-induced expression of hsp-70 declines with age. It has also been shown that a cellular protein, heat shock factor (HSF), which binds to the heat shock element (HSE) in the promoter region of the hsp-70 gene, is induced in the adrenal after restraint stress. Whether the induction of HSF alters with age needs to be studied.
HSP60 in cancer: a promising biomarker for diagnosis and a potentially useful target for treatment
Published in Journal of Drug Targeting, 2022
Bo Sun, Ganghui Li, Qing Yu, Dongchun Liu, Xing Tang
Heat shock proteins (HSPs), many of which are chaperones, are highly conserved proteins whose function is to reverse or inhibit the denaturation or unfolding of cellular proteins under stress or high temperature [1]. HSPs were originally investigated as a group of proteins induced by heat stress; however, it is now known that their expression can also facilitate protein folding and maintenance of natural structures and functions of other proteins under ultraviolet light, wound healing, tissue remodelling, pathogens, cancer and more [1]. HSPs families are classified into six groups (HSP100, HSP90, HSP70, HSP60, HSP40 and small HSP (sHSP)) according to their molecular weight [2]. Except for the group of sHSP, HSP proteins are ATP-dependent proteins with ATPase activity [3]. Heat shock factor (HSF) can regulate the synthesis of HSPs; under conditions of stress, HSF forms a trimer, enters the nucleus from the cytoplasm, and undergoes phosphorylation in the nucleus, thereby promoting the synthesis of thermal shock proteins [4].
ASK1 and its role in cardiovascular and other disorders: available treatments and future prospects
Published in Expert Review of Proteomics, 2019
Mohammad Hassan Baig, Abu Baker, Ghulam M Ashraf, Jae-June Dong
It is well explored that expression of heat shock transcription factor 1 (HSF-1) is one of the major regulators of heat response and is well known to be involved in protection against cardiovascular diseases, including ischemia. ASK1 negatively regulates HSF-1 expression, and it is found that the expression of ASK1 inhibits the overexpression of HSF-1 [77,78]. It has been reported that in H2O2-induced cardiomyocyte death, the expression of ASK1 is negatively regulated by HSF-1. There are several other findings that provide sufficient evidence of the involvement of ASK1 in the pathogenesis of myocardial IRI. For instance, it has been found that in aging animals increased nitration of Trx is responsible for IR-induced cardiomyocyte apoptosis and an increased infarct size, as compared to their younger counterparts [79]. This increase in nitration of Trx disrupts the formation of the ASK1-Trx complex in aging hearts.
Skeletal muscle cold shock and heat shock protein mRNA response to aerobic exercise in different environmental temperatures
Published in Temperature, 2019
Rebecca L. Cuthbert, Robert J. Shute, Dustin R. Slivka
The response of heat shock proteins 70, 27, and 90 (HSP70, HSP27, HSP90) in skeletal muscle tissue to exercise or temperature in humans has been studied extensively. Heat shock proteins increase when exposed to temperatures up to 44°C [11,12], whereas exposure to cold shock produces a decrease in heat shock protein content [13]. There are different responses when comparing trained and untrained individuals, as well as when comparing the intensity and type of aerobic exercise performed by trained individuals. Exercise that causes damage to skeletal muscle tissue, specifically eccentric contractions, triggers an increase in HSP27 and HSP70 mRNA [14–17]. Similarly, HSP70 mRNA increases in untrained individuals after moderate aerobic exercise [18–20], but only after high intensity aerobic training in trained individuals [21]. The response of heat shock factor-1 (HSF1), the primary activator of heat shock proteins, similarly depends on the severity and type of stress the subject is exposed to [22]. A slight increase in HSF1 in response to exercise in humans may be detected even in the absence of an effect on the other heat shock proteins. It is not clear if cold shock proteins have a similar response to exercise and temperature as heat shock proteins or if these stress proteins respond to the stress in a temperature dependent manner as their names suggest.