Disease relevance of Heat Stress Disorders

• Cell survival after subsequent lethal heat stress or simulated ischemia was assessed using trypan blue exclusion and released lactate dehydrogenase activity [1].
• Myocardial ischemia markedly increases the expression of several members of the stress/heat shock protein (HSP) family, especially the inducible HSP70 isoforms [2].
• When mouse testis was exposed to heat stress by experimental cryptorchidism, the level of Rbm3 was decreased in Sertoli cells [3].
• These findings suggest that the WAF1 expression is heat-inducible in human glioblastoma cells and that this induction may be due to signal transduction mediated by p53 in response to heat stress [4].
• Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis [5].

High impact information on Heat Stress Disorders

• Expression of the UBI4 gene is similarly induced by either heat stress or starvation [6].
• The heat stress signal is thought to be transduced to HSF by changes in the physical environment, in the activity of HSF-modifying enzymes, or by changes in the intracellular level of heat shock proteins [7].
• HSF is present in a latent state under normal conditions; it is activated upon heat stress by induction of trimerization and high-affinity binding to DNA and by exposure of domains for transcriptional activity [7].
• These findings suggest an unforeseen role for HSF as a repressor of normal gene activity during heat stress [8].
• Prevention of protein denaturation under heat stress by the chaperonin Hsp60 [9].

Chemical compound and disease context of Heat Stress Disorders

• Thermotolerance in CS protoplasts was restored by plasmid-borne HsfA2, resulting in expression of chaperones, thermoprotection of firefly luciferase, and assembly of heat stress granules [10].
• Immunoblot analysis with antiserum against HSF1 demonstrated that the steady-state level of HSF1 was not changed in glutathione-depleted cells, but glutathione depletion inhibited the nuclear translocation of HSF1 after exposure to heat stress [11].
• Specific induction of the 70-kD heat stress proteins by the tyrosine kinase inhibitor herbimycin-A protects rat neonatal cardiomyocytes. A new pharmacological route to stress protein expression [1]?
• The effect of heat stress on glycolytic and mitochondrial pathways was examined by measuring contractile performance in the presence of glucose and pyruvate, respectively [12].
• RESULTS: In the perfused liver, cholyltaurine transport was reduced by 59% by endotoxin, but transport was not reduced when heat stress was applied 2 hours before injection of lipopolysaccharide [13].

Biological context of Heat Stress Disorders

• Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress [14].
• The dinucleotide AppppA (5',5'''-P1, P4-diadenosine tetraphosphate) is rapidly synthesized in cells exposed to heat stress or oxidative stress [15].
• We examined the effects of deletions of genes encoding deadenylase components Ccr4p and Pan2p and putative RNA-binding proteins Pub1p and Puf4p on the genome-wide pattern of mRNA stability after inhibition of transcription by chemicals and/or heat stress [16].
• Furthermore, inhibition of HSF1/hsp70 was accompanied by an increase in apoptosis rates from 20% to 50% in response to heat stress [17].
• This overview summarizes recent data on sphingolipid function in cell signalling, their role in the heat-stress response and Ca(2+) homeostasis, and addresses their function in transport of glycosylphosphatidylinositol-anchored proteins [18].

Anatomical context of Heat Stress Disorders

• The mitochondrial heat shock protein 60 (Hsp60) has now been shown to form complexes with a variety of polypeptides in organelles exposed to heat stress [9].
• In particular, we show that mt-Hsp70 acts in maintaining the var1 protein, the only mitochondrially encoded subunit of mitochondrial ribosomes, in an assembly competent state, especially under heat stress conditions [19].
• We have previously reported that intracellular tumor necrosis factor (enTNF) is responsible for resistance, in established cell lines to doxorubicin (DOX), exogenous TNF, and heat stress by inducing manganous superoxide dismutase (MnSOD), thereby scavenging reactive oxygen free radicals [20].
• However, immune-purification of p56 from normal and heat-stressed cytosols with the EC1 monoclonal antibody results in the presence of a 56-kDa protein that exhibits an increased rate of synthesis in response to heat stress [21].
• A maize (Zea mays L.) small heat shock protein (HSP), HSP22, was previously shown to accumulate to high levels in mitochondria during heat stress [22].

Gene context of Heat Stress Disorders

• Reactivation of mitochondrial protein synthesis after heat stress depends on the presence of Hsp78, though Hsp78 does not confer protection against heat-inactivation to this process [23].
• Transformation of the soybean Hsp101 gene into a yeast HSP104 deletion mutant complemented restoration of acquired thermotolerance, a process in which cells survive an otherwise lethal heat stress after they are given a permissive heat treatment [24].
• By contrast, expression of the FKB1 gene, which encodes a cytoplasmic member of the yeast FKBP family, is neither heat responsive nor necessary for survival after exposure to heat stress [25].
• Heat stress regulation of human heat shock genes is mediated by human heat shock transcription factor hHSF1, which contains three 4-3 hydrophobic repeats (LZ1 to LZ3) [26].
• Significantly, the interaction between Ubc4 and the proteasome is strongly induced by heat stress, consistent with the requirement for this E2 for efficient stress tolerance [27].

Analytical, diagnostic and therapeutic context of Heat Stress Disorders

• Northern blot analysis demonstrated an increase in heat stress protein (HSP) 70 mRNA 2 h after the preconditioning ischemia; at this same time point, immunohistochemical analysis revealed a concentration of HSP70 in the nucleus and an overall increase in staining for HSP70 [28].
• Blocking heat stress-induced HSP-70 with siRNA did not significantly block the protective effect of heat stress against cold storage and rewarming cell death; however, overexpression of HSP-70 protected HK-2 cells from this stress [29].
• Perfusion of hearts taken 48 h after heat stress with 75 microM hydrogen peroxide resulted in the same effect on mechanical dysfunction, coronary resistance, lactate dehydrogenase release, and cardiac glutathione depletion as sham controls [30].
• CONCLUSION: These results demonstrate that the myocardial protective effect induced by heat stress could extend to a pathological animal model like the transgenic [(mREN-2)27] hypertensive rat and is correlated with a myocardial HSP72 induction [31].
• We investigated the effects of sublethal heat stress in murine cortical cell cultures exposed to combined oxygen and glucose deprivation [32].

References