Disease relevance of Hsf1

• Following heat stress, hearts from aged animals demonstrated a 47% reduction in Hsf1 activation, a reduction in Hsp72 mRNA and a 35% reduction in Hsp72 protein content, compared to hearts from adults [1].
• Hyperthermia resulted in stress-induced Hsf1 hyperphosphorylation in cochlea as well as cerebellum [2].
• While HSP70i expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSF1 mRNA remained constitutively expressed under all conditions [3].
• Ischemia-reperfusion injury is known to induce the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72) mainly via rapid activation of heat shock transcription factor 1 (HSF1) [3].
• Here we provide evidence that this induction is mediated through the activation of heat shock transcription factor 1 in response to high blood pressure [4].

High impact information on Hsf1

• HSF1 activation was completely blocked by hemoglobin, dithiothreitol, and cycloheximide, suggesting that the protein damage and nascent polypeptide formation induced by NO may initiate this activation [5].
• Although the activation of HSF during global ischemia was weak and rapidly attenuated, postischemic reperfusion induced a significant activation of HSF [6].
• The levels of the heat shock transcription factor in nuclear extracts isolated from heat-shocked hepatocytes were measured in a gel shift assay [7].
• Activation of heat shock transcription factor (HSF) (by electrophoretic mobility shift assay), heat shock protein 70 (HSP70), and glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA (by reverse transcription polymerase chain reaction [RT-PCR]), as well as HSP70 (by Western blot) were investigated in freeze-clamped liver samples [8].
• In conclusion, we showed the cGMP-mediated activation of HSF by ANP, which resulted in elevated HSP70 mRNA and protein concentrations and correlated with enhanced binding of HSP70 to IkappaB [8].

Chemical compound and disease context of Hsf1

• Previously, we reported that prolactin (PRL)-dependent Nb2 lymphoma cells exhibit an aberrant heat shock response because of cysteine protease-mediated fragmentation of the heat shock transcription factor (HSF) [9].

Biological context of Hsf1

• Reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry were used to examine the expression and localization of Hsf1, the stress-responsive member of the Hsf family, in the rat and mouse cochlea [2].
• Thus, we conclude that during ischemia-reperfusion in rat kidneys, the heat shock response is regulated by other means than expressional changes of HSF1 [3].
• Gel retardation assays demonstrated maximal HSF activation 10 days after ovulation [10].
• To determine whether HSF proteolysis occurred as a generalized phenomenon associated with apoptosis, the effects of other activators of this process were evaluated [9].
• However, the current study does not support previous observations regarding major changes in HSF1 phosphorylation and suggests that other PKA-related mechanisms mediate the activation of Hsp70 gene expression following exercise [11].

Anatomical context of Hsf1

• Semi-quantitative RT-PCR of cochlear RNA revealed that Hsf1 was more highly expressed in a subfraction containing sensorineural epithelium and lateral wall than in a subfraction containing modiolus, with the alpha splice form predominant over the beta in both subfractions [2].
• Hsf1 immunostaining was found in the nuclei of inner and outer hair cells in the organ of Corti, spiral ganglion cells in the modiolus, and cells in the marginal and intermediate layers of the stria vascularis [2].
• A number of pharmacological and physiological inhibitors of luteal cell function stimulate HSP-70 synthesis via activation of the heat shock transcription factor (HSF) [10].
• Therefore, it appears that the reduced ability of lymphocytes from old rats to express hsp70 in response to a heat shock occurs at the level of transcription because of an alteration in the ability of the heat shock transcription factor to bind the HSE on the promoter of the hsp70 gene [12].
• However, the thermostability of the DNA binding activity of HSF1 was significantly reduced with age in a cell-free system as well as in isolated hepatocytes [13].

Associations of Hsf1 with chemical compounds

• Gel-retardation assays demonstrated HSF activation within 7.5 min after PGF2 alpha (400 micrograms) administered in vivo [10].
• In afterloaded hearts, with the perfusion of norepinephrine, the activation of HSF was not induced [14].
• Gel mobility shift assays revealed that each prostaglandin prolonged the arsenite-induced binding of HSF to HSE [15].
• Cells exposed to 10 microM each of prostaglandin A1, A2, or J2 for 1 h resulted in stimulation of the binding to the heat shock element (HSE) of heat shock transcription factor (HSF) [15].
• We examined the induction of the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during increased preload of left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin [14].

Other interactions of Hsf1

• GSK3, which may act downstream to PI3-kinase through AKT, undergoes hyperphosphorylation, thus playing a possible role in the protection from apoptosis and in the modulation of heat-shock transcription factor activity [16].

Analytical, diagnostic and therapeutic context of Hsf1

• Hsf1 activation following heat shock was examined by Western blot [2].
• Activation of heat-shock transcription factor (HSF) was detected by gel retardation assay and transcription was confirmed by Northern analysis [17].
• Binding of the heat shock transcription factor to the heat shock element decreased with age and was significantly higher in hepatocyte extracts isolated from old rats fed the caloric restriction diet than in those from old rats fed ad libitum [7].
• During continuous perfusion ANP as well as 8-Br-cGMP activated HSF, HSP70 protein concentrations paralleled HSF-activation [8].
• In the heart of transgenic mice overexpressing a constitutively active form of HSF1, ischemia followed by reperfusion-induced ST-segment elevation in ECG was recovered faster, infarct size was smaller, and cardiomyocyte death was less than wild-type mice [18].

References