Synthesis Of Hsps Research Articles

Activities of antioxidant enzymes and Hsp levels in response to elevated temperature in land snail species with varied latitudinal distribution.

Land snails occupy a variety of habitats, with differing temperature and humidity regimes and exhibit a wide span of adaptations, to withstand abiotic condition changes. The present work's aim was to examine the correlation of habitat's thermal adversity in different Mediterranean type habitats with the land snail's antioxidant and heat shock responses. For this purpose, snails of different species from populations along a north-south axis from the islands and mainland of Greece were exposed to elevated temperature and antioxidant enzyme activities, and Hsp70 and Hsp90 levels were determined in their tissues. The ATP, ADP, and AMP levels and the adenylate energy charge (AEC) were also determined. The comparison of protein levels and enzymatic activities across time intervals revealed significant differences for all factors examined. While the gradation pattern over time for a given factor was similar in all populations the absolute values over time differed. Catalase activity and the Hsp90 protein levels had the higher contribution in separating the different species and populations, followed by the activity of glutathione reductase and Hsp70 protein levels which contributed to a lesser degree. In general, populations from the southern part of their distribution in Greece tend to display a faster increase than northern populations in induction levels of all factors examined. Our data seem to be in line with the concept of preparation for oxidative stress (POS) while the changes in the AEC indicate an early preparation to cover the energy demand for the induction and synthesis of antioxidant enzymes and Hsps.

Impacts of Heat Stress on Wheat: A Critical Review

A brief review is given of investigations on stress-induced alterations in the yield of different biochemical contents in wheat. Wheat is major cereal crop for fulfilling the calories demands of growing population. Alterations in the worldwide climate are predicted to have critical sentence for crop production. Abiotic stresses such as heat and drought are major abiotic stresses restraining crop production. Heat stress reduces wheat growth by upsetting various physiological and biochemical processes and the developmental stage of the plant is critical in demonstrating the vulnerability of various species and cultivars subjected to high temperature. Heat stress did not affect the protein content but there is strong correlation between leaf nitrogen content and grain protein content. Induction of HSPs seems to be the universal response and adaptation to temperature stress. The synthesis of HSPs is believed to play significant role either in preventing or minimizing the adverse effects of high temperature both at molecular and cellular levels. Wheat has the tendency to adopt diverse types of responses to temperature stress as well as a heat shock by developing thermo-tolerance for the enhancement of the grain quality and yield.

Effects of salinity on growth, fatty acid synthesis, and expression of stress response genes in the cyclopoid copepod Paracyclopina nana

In marine ecosystems, salinity fluctuations are critical in modulating energy balance, inducing stress proteins, providing reproductive success and affecting the distribution of copepods. Salinity induces osmotic stress in organisms when they are not in their optimal condition and the stressful status increase the energy demand required for osmoregulation, which in turn reflects in all biological processes. Effects of salinity stress on life history traits and tolerance are species-specific. In this study, we used the estuarine cyclopoid copepod Paracyclopina nana to understand the responses towards the hypo (5ppt) and hypersalinity (25 and 30ppt) conditions, and compared that with the control (15ppt). We investigated the life cycle parameters (e.g. growth and fecundity), fatty acid (FA) synthesis, lipid accumulation (as lipid droplets [LDs]) and modulation of heat shock proteins (hsps) in response to salinity stress. As a result, life cycle parameters and FA synthesis, LDs, and modulation of hsps were found highly dependent on salinity changes in P. nana. Particularly, hypersalinity resulted in developmental retardation, reduced fecundity, decreased FA synthesis, a drop in lipid accumulation, and modulation of stress response proteins, suggesting that P. nana devoted increased energy to cope with the osmotic imbalance due to salinity stress in hypersalinity conditions. This finding provides a better understanding of how salinity affects in vivo endpoints and the relevant molecular responses in estuarine copepods. Statement of relevanceWe envisage that this manuscript will be helpful to understand salinity-dependent lipid composition changes in copepods and optimize the optimal salinity for the mass culture for this species.Considering the small size (~600μm) of P. nana and its potential as live feeds for finfish larviculture, the present findings have considerable importance for the aquaculture industry.

Cold tolerance in rice germinating seeds revealed by deep RNAseq analysis of contrasting indica genotypes

Rice productivity is largely affected by low temperature, which can be harmful throughout plant development, from germination to grain filling. Germination of indica rice cultivars under cold is slow and not uniform, resulting in irregular emergence and small plant population. To identify and characterize novel genes involved in cold tolerance during the germination stage, two indica rice genotypes (sister lines previously identified as cold-tolerant and cold-sensitive) were used in parallel transcriptomic analysis (RNAseq) under cold treatment (seeds germinating at 13°C for 7 days). We detected 1,361 differentially expressed transcripts. Differences in gene expression found by RNAseq were confirmed for 11 selected genes using RT-qPCR. Biological processes enhanced in the cold-tolerant seedlings include: cell division and expansion (confirmed by anatomical sections of germinating seeds), cell wall integrity and extensibility, water uptake and membrane transport capacity, sucrose synthesis, generation of simple sugars, unsaturation of membrane fatty acids, wax biosynthesis, antioxidant capacity (confirmed by histochemical staining of H2O2), and hormone and Ca2+-signaling. The cold-sensitive seedlings respond to low temperature stress increasing synthesis of HSPs and dehydrins, along with enhanced ubiquitin/proteasome protein degradation pathway and polyamine biosynthesis. Our findings can be useful in future biotechnological approaches aiming to cold tolerance in indica rice.

Inhibition of HSP70 reduces porcine reproductive and respiratory syndrome virus replication in vitro

BackgroundSuccessful viral infection requires the involvement of host cellular factors in their life cycle. Heat shock protein 70 (HSP70) can be recruited by numerous viruses to promote the folding, maturation, or assembly of viral proteins. We have previously shown that HSP70 is significantly elevated in porcine reproductive and respiratory syndrome virus (PRRSV)-infected lungs, suggesting HSP70 may play a potential role during PRRSV infection. In this study, we tried to investigate the role of HSP70 during PRRSV infection.ResultsIn this study, we observed that PRRSV infection induced the expression of HSP70. The down-regulation of HSP70 using quercetin, a HSPs synthesis inhibitor, or small interfering RNAs (siRNA) reduced the viral protein level and viral production. Notably, these inhibitory effects on PRRSV infection could be attenuated by heat shock treatment. In addition, HSP70 was found to colocalize with the viral double-stranded RNA (dsRNA) and knockdown of HSP70 decreased the dsRNA levels, suggesting HSP70 is involved in the formation of viral replication and transcription complex (RTC) and thus affects the viral replication.ConclusionsOur study revealed that HSP70 is an essential host factor required for the replication of PRRSV. The inhibition of HSP70 significantly reduced PRRSV replication, which may be applied as an effective antiviral strategy.

Sea urchin embryos exposed to cadmium as an experimental model for studying the relationship between autophagy and apoptosis

The sea urchin embryo is a suitable model that offers an excellent opportunity to investigate different defence strategies activated in stress conditions. We previously showed that cadmium accumulates in a dose- and time-dependent manner into embryonic cells, activating different stress and defence mechanisms, including the synthesis of HSPs and the onset of apoptosis and/or autophagy. In this paper we investigated the functional relationship between autophagy and apoptosis, evaluating apoptosis signals in cadmium-exposed Paracentrotus lividus embryos with inhibited autophagy. We found that the inhibition of autophagy produced the concurrent reduction of apoptosis, suggesting that the two phenomena are functionally related. Considering the catabolic role of autophagy, an energetic hypothesis to explain the relationship was evaluated. Using a substrate for ATP production, we found that apoptosis, assessed by TUNEL and cleaved caspase-3 immunocytochemistry, was substantially restored in cadmium-treated embryos where autophagy was inhibited by 3-Methyladenine. On the basis of these results, we propose that, autophagy could play a crucial role in stress response of this organism because autophagy could energetically contribute to apoptotic execution through its catabolic role.

Elevated cortisol modulates Hsp70 and Hsp90 gene expression and protein in sea bass head kidney and isolated leukocytes

In fish, interactions between Hsps and cortisol are involved in stress modulated physiological processes including innate immune responses. Cortisol exerts a role in the regulation of Hsps synthesis. Fish head kidney is a lymphomieloid and endocrine organ releasing cortisol, and it is the central organ for immune-endocrine interactions. In sea bass, cortisol intraperitoneal injection and in vitro treatment of head kidney cells show that inducible Hsp70 and Hsp90 are modulated by this hormone. However, an inverse relationship between mRNA expression (real-time PCR) and Hsp70 and Hsp90 protein levels (densitometric band analysis) was found. Time-course assays indicate a cortisol-mediated regulation. Furthermore, Hsp70 gene modulation appears to be more susceptible to the cortisol action and the mRNA was transcribed within 3 h post-injection. The restoration of the homeostatic conditions was observed at a week p.i., when plasma cortisol baseline was reached. Although fish manipulation and injection exerted stressing effects as indicated by serological parameters, differences between cortisol treated specimens compared to untreated or sham fish are statistically significant. Similar results were found by examining in vitro total cells and isolated leukocytes from head kidney cultured for 3 h with increasing cortisol concentration. Finally, MTT test and DNA fragmentation experiments showed that the apoptotic effect expected in cortisol-treated cells could be counteracted by high Hsp70 intracellular levels.

Advance in O-GlcNAc modification and its cardiovascular protective effects

Background O-linked attachment of the monosaccharide-N -acetylglucosamine(O-GlcNAc) is a highly dynamic and ubiquitous posttranslational protein modification, plays a critical role in regulating numerous biological processes. O -GlcNAc transferase and O-GlcNAcase are responsible for the addition and removal of O-GlcNAc from serine/threonine residues, respectively. Objective To review the potential mechanisms of O -GlcNAc modification and the target protein. Content Main potential mechanisms of O-GlcNAc modification include antagonizing inflammatory, increasing synthesis of HSPs, inhibiting apoptosis, etc. Trend Further insights into the signal pathway of O -GlcNAc modification may provide a nice prospect for the therapy of cardiovascular dysfunction. Key words: O-GlcNAc modification; Cardiovascular protection; Anti-inflammatory; Heat shock proteins; Anti-apoptosis

The similia principle: Results obtained in a cellular model system

This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized.

Effect of gamma radiation on heat shock protein expression of four foodborne pathogens

The effects of gamma radiation on three heat shock proteins (Hsps) (GroEL, DnaK and GroES) synthesis in two Gram-negative (Escherichia coli and Salmonella serotype Typhimurium) and two Gram-positive (Staphylococcus aureus and Listeria monocytogenes) bacteria were investigated. The bacterial strains were treated with three radiation doses to induce cell damage, to obtain a viable but nonculturable state, and to cause cell death. Western blot analysis and quantification of Hsps in bacteria were performed immediately after irradiation treatment. In the four foodborne pathogens, GroEL was strongly induced by gamma rays in a dose-dependent manner, confirming the involvement of this protein in the cellular response to the stress generated by ionizing radiation. In addition, it was found that E. coli exposed to gamma radiation showed a significantly induction of DnaK and GroES proteins when compared with nonirradiated bacteria, whereas a GroES slight induction and a DnaK inhibition were observed in Salm. Typhimurium. The gamma rays influence the synthesis of Hsps in foodborne pathogen in a way that critically depends on the radiation dose. The study of stress response to several radiation doses was undertaken to elucidate how bacteria can survive in harsh conditions and cope with gamma radiation used to control foodborne pathogens and to characterize their adaptative response to this treatment.

Hsp70 response to 5-fluorouracil treatment in human colon cancer cell lines

Colorectal cancer is a common disease with high rate of mortality. Although there is evidence of some benefits of 5-fluorouracil (5-FU), the most commonly used drug in colon cancer therapy, it still remains unsatisfactory because of intrinsic or acquired drug resistance. Heat shock proteins (Hsps) synthesis can be increased by cellular insults, such as chemotherapy-induced damage. Inducible Hsp70 has been suggested to be involved in cytoprotection against apoptosis. In the present study, we investigated whether the content of Hsp70 is associated to 5-FU resistance. HT-29 and SNU-C4 human colon cancer cell lines were treated with 5-FU and their relative chemoresistance, and Hsp70 were determined. Comparison of IC(50) values showed that the HT-29 cells were relatively resistant to 5-FU, whereas the SNU-C4 cells presented greater sensitivity to this drug. Further, 5-FU treatment leads to a hypodiploid population in HT-29 cells significantly lower compared to SNU-C4 cells. In the HT-29 cell line, 5-FU treatment promoted an increase of 5.5 times in Hsp70 concentration after 12 h. Then, within 24 h, the increase in Hsp70 levels was still about two times. In contrast, in the SNU-C4 cell line, 5-FU induced an increase of about two times in the Hsp70 content after 12 h and, after 24 h, did not significantly affect Hsp70 content. These data suggest that 5-FU induced Hsp70 synthesis in the HT-29 resistant cell line and that this Hsp70 accumulation could protect against 5-FU-induced apoptosis. Thus, Hsp70 protection against 5-FU-induced apoptosis might underlie colon cancer chemoresistance.

Translocation of constitutively expressed heat shock protein Hsc70 to synapse‐enriched areas of the cerebral cortex after hyperthermic stress

Hsp70 is a multi-gene family composed of stress-inducible members (Hsp70) and other members that are constitutively expressed (Hsc70). The heat shock proteins Hsp70 and Hsc70 exhibit similar molecular structure and biochemical functions. Constitutively expressed Hsc70 is enriched in the mammalian nervous system compared with non-neural tissues and present at high levels in neuronal cell bodies. After thermal stress, Hsc70 is translocated to synapse-enriched areas of the cerebral cortex where it associates with Hsp40 to form a complex that can refold denaturated proteins. These results suggest that the heat shock response in the nervous system involves not only the synthesis of stress-inducible Hsps but also the translocation of constitutively expressed Hsc70 to synapse-enriched areas where it could participate in neuroprotective mechanisms that preserved synaptic function during times of stress.

Continuous up-regulation of heat shock proteins in larvae, but not adults, of a polar insect

Antarctica's terrestrial environment is a challenge to which very few animals have adapted. The largest, free-living animal to inhabit the continent year-round is a flightless midge, Belgica antarctica. Larval midges survive the lengthy austral winter encased in ice, and when the ice melts in summer, the larvae complete their 2-yr life cycle, and the wingless adults form mating aggregations while subjected to surprisingly high substrate temperatures. Here we report a dichotomy in survival strategies exploited by this insect at different stages of its life cycle. Larvae constitutively up-regulate their heat shock proteins (small hsp, hsp70, and hsp90) and maintain a high inherent tolerance to temperature stress. High or low temperature exposure does not further up-regulate these genes nor does it further enhance thermotolerance. Such "preemptive" synthesis of hsps is sufficient to prevent irreversible protein aggregation in response to a variety of common environmental stresses. Conversely, adults exhibit no constitutive up-regulation of their hsps and have a lower intrinsic tolerance to high temperatures, but their hsps can be thermally activated, resulting in enhanced thermotolerance. Thus, the midge larvae, but not the adults, have adopted the unusual strategy of expressing hsps continuously, possibly to facilitate proper protein folding in a cold habitat that is more thermally stable than that of the adults but a habitat subjected frequently to freeze-thaw episodes and bouts of pH, anoxic, and osmotic stress.

Heat shock proteins protect both MPP + and paraquat neurotoxicity

The exposure of immortalized rat neuroblast cells to MPP + and paraquat results in cell death. Heat shock pre-treatment prior to the addition of MPP + and paraquat significantly reduced cell death and led to an increase in the synthesis of Hsp27 and Hsp70 proteins. Quercetin inhibits the synthesis of heat shock proteins (Hsp) and prevents their protective effect, which suggests that this protection was dependent on the Hsps synthesis. These data indicate that heat shock protects cells from the toxic effect of MPP + and paraquat. These results and the structural similarity between paraquat and MPP + support the role of paraquat as a putative risk factor in the etiology of Parkinson's disease.

Do mitochondria regulate the heat-shock response in Saccharomyces cerevisiae?

A mild heat shock induces the synthesis of heat-shock proteins (hsps), which protect cells from damage during more extreme heat exposure. The nature of the signals that induce transcription of heat shock-regulated genes remains conjectural. In this work we studied the role of mitochondria in regulating hsps synthesis in Saccharomyces cerevisiae. The results obtained clearly indicate that a mild heat shock elicits a hyperpolarization of the inner mitochondrial membrane and such an event is one of several signals triggering the chain of reactions that activates the expression of the HSP104 gene and probably the expression of other heat shock-regulated genes in S. cerevisiae. The uncouplers or mitochondrial inhibitors which are capable of dissipating the potential on the inner mitochondrial membrane under particular experimental conditions prevent the synthesis of Hsp104 induced by mild heat shock and thus inhibit the development of induced thermotolerance. It is suggested that cAMP-dependent protein kinase A is participating in the mitochondrial regulation of nuclear genes.

Radioresistance is associated to increased Hsp70 content in human glioblastoma cell lines

Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo apoptosis. Heat-shock proteins (Hsps) synthesis can be increased by cellular insults, such as radiation-induced damage. Inducible Hsp70 has been suggested to have multiple roles in cytoprotection against apoptosis. Accordingly, high levels of Hsp70 prevent stress-induced apoptosis. In the present study, we investigated whether the content of Hsp70 is associated to glioblastoma cell radioresistance. To this end, the U-87MG, U-251MG and MO59J human glioblastoma cell lines were irradiated at 2, 5 and 10 Gy and their relative radioresistance and Hsp70 were determined. Following 5 Gy irradiation, in MO59J and U-251MG a significant decrease in colony formation was found, whereas the U-87MG was relatively radioresistant. Three hours after the irradiation (at 5 Gy) Hsp70 contents increased 110% in the U-87 MG cells, but did not significantly change in the U-251MG and MO59J cells. Thus, our results suggest that Hsp70 protection against radiation-induced apoptosis might underlie glioblastoma radioresistance.

Commonly used antibiotics induce expression of Hsp 27 and Hsp 60 and protect human lymphocytes from apoptosis

Heat shock proteins (Hsps) are abundant molecular chaperones participating in the cytoprotection. The kinetics of synthesis of Hsps closely correlates with the kinetics of development of resistance to cell death. In this study, we analysed the probable involvement of Hsp 27 and Hsp 60 in the protection of cells undergoing apoptosis. Human lymphocytes cultured in the presence of ampicillin or ceftriaxone produced Hsp 60 and Hsp 27, estimated by immunoblotting in a time-dependent manner and the increased levels of Hsp 60 and Hsp 27 correlated with enhanced resistance of the lymphocytes to apoptosis, as determined by flow cytometry. Cultures treated with ampicillin or ceftriaxone also exhibited smaller numbers of apoptotic cells than untreated cultures when exposed to the apoptosis-inducing agent staurosporine (1 mM). In contrast, cloramphenicol induced the production of only small amounts of Hsp 60, and no resistance apoptosis. Further studies are needed to clarify the potential role of Hsp 27 and Hsp 60 in the resistance of human cells to apoptosis and the effects of antibiotics on this phenomenon.

Commonly used antibiotics induce expression of Hsp 27 and Hsp 60 and protect human lymphocytes from apoptosis

Heat shock proteins (Hsps) are abundant molecular chaperones participating in the cytoprotection. The kinetics of synthesis of Hsps closely correlates with the kinetics of development of resistance to cell death. In this study, we analysed the probable involvement of Hsp 27 and Hsp 60 in the protection of cells undergoing apoptosis. Human lymphocytes cultured in the presence of ampicillin or ceftriaxone produced Hsp 60 and Hsp 27, estimated by immunoblotting in a time-dependent manner and the increased levels of Hsp 60 and Hsp 27 correlated with enhanced resistance of the lymphocytes to apoptosis, as determined by flow cytometry. Cultures treated with ampicillin or ceftriaxone also exhibited smaller numbers of apoptotic cells than untreated cultures when exposed to the apoptosis-inducing agent staurosporine (1 mM). In contrast, cloramphenicol induced the production of only small amounts of Hsp 60, and no resistance apoptosis. Further studies are needed to clarify the potential role of Hsp 27 and Hsp 60 in the resistance of human cells to apoptosis and the effects of antibiotics on this phenomenon.

Translational Thermotolerance Provided by Small Heat Shock Proteins Is Limited to Cap-dependent Initiation and Inhibited by 2-Aminopurine

Heat shock results in inhibition of general protein synthesis. In thermotolerant cells, protein synthesis is still rapidly inhibited by heat stress, but protein synthesis recovers faster than in naive heat-shocked cells, a phenomenon known as translational thermotolerance. Here we investigate the effect of overexpressing a single heat shock protein on cap-dependent and cap-independent initiation of translation during recovery from a heat shock. When overexpressing alphaB-crystallin or Hsp27, cap-dependent initiation of translation was protected but no effect was seen on cap-independent initiation of translation. When Hsp70 was overexpressed however, both cap-dependent and -independent translation were protected. This finding indicates a difference in the mechanism of protection mediated by small or large heat shock proteins. Phosphorylation of alphaB-crystallin and Hsp27 is known to significantly decrease their chaperone activity; therefore, we tested phosphorylation mutants of these proteins in this system. AlphaB-crystallin needs to be in its non-phosphorylated state to give protection, whereas phosphorylated Hsp27 is more potent in protection than the unphosphorylatable form. This indicates that chaperone activity is not a prerequisite for protection of translation by small heat shock proteins after heat shock. Furthermore, we show that in the presence of 2-aminopurine, an inhibitor of kinases, among which is double-stranded RNA-activated kinase, the protective effect of overexpressing alphaB-crystallin is abolished. The synthesis of the endogenous Hsps induced by the heat shock to test for thermotolerance is also blocked by 2-aminopurine. Most likely the protective effect of alphaB-crystallin requires synthesis of the endogenous heat shock proteins. Translational thermotolerance would then be a co-operative effect of different heat shock proteins.

Wound‐induced PAL activity is suppressed by heat‐shock treatments that induce the synthesis of heat‐shock proteins

Wounding lettuce leaves induces the de novo synthesis of phenylalanine ammonia‐lyase (PAL, EC 4.3.1.5), the accumulation of phenolic compounds, and subsequent tissue browning. A brief heat‐shock at 45°C reduces the rise in wound‐induced PAL, the accumulation of phenolic compounds, and tissue browning. The activity of PAL measured 24 h after wounding and the content of phenolic compounds (absorbance of methanol extract at 320 nm) measured 48 h after wounding was highly correlated (R2 > 0.90) in tissue developing the normal wound response and in tissue subjected to 0–180 s of heat‐shock after wounding. The synthesis of a unique set of proteins called heat‐shock proteins (hsps) is induced by these heat‐shock treatments. Western‐blot analyses of proteins isolated from wounded and heat‐shocked Iceberg and Romaine lettuce mid‐rib leaf tissue was done using antibodies against hsp 23. Only those heat‐shock treatments that were effective at inducing the synthesis of hsp 23 were effective in reducing the activity of PAL induced by wounding and the subsequent accumulation of phenolic compounds. Hsps induced in non‐wounded, whole leaves by exposure to 45°C for 150 s did not significantly interact with PAL previously synthesized in non‐heat‐shocked wounded leaves to limit its activity. The preferential synthesis of hsps over that of wound‐induced PAL, rather than the presence of hsps, may be responsible for the ability of a heat‐shock treatment to reduce the wound‐induced increase in PAL activity. Our results support this novel concept, and the possibility that heat‐shock treatments can have significant physiological effects on the response of the tissue to other stresses, not because of the specific genes they induce or repress, or the products they cause to be synthesized, but by their secondary action of influencing the synthesis of other proteins (e.g. PAL) by the suppression of non‐hsps protein synthesis.