• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.64-71
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• 2022

Norovirus (NV) is the most common cause of viral gastroenteritis, with the potential to develop into a fatal disease in those who are immuno-compromised, and effective vaccines and treatments are still non-existent. In this study, we aimed to elucidate the molecular mechanism of the previously identified NV replication inhibitor utilizing a vinyl-stilbene backbone, AC-1858. First, we confirmed the inhibition of the NV RNA replication by a structural analog of AC-1858, AC-2288 with its exclusive cytoplasmic sub-cellular localization. We further validated the induction of one specific host factor, the phosphorylated form of heat shock factor (HSF)-1, and its increased nuclear localization by AC-1858 treatment. Finally, we verified the positive and negative impact of the siRNA-mediated downregulation and lentivirus-mediated overexpression of HSF-1 on NV RNA replication. In conclusion, these data suggest the restrictive role of the host factor HSF-1 in overall viral RNA genome replication during the NV life cycle.

• Bulletin of the Korean Chemical Society
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• v.33 no.12
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• pp.4201-4203
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• 2012

• Journal of Animal Environmental Science
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• v.20 no.4
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• pp.147-154
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• 2014

Heat stress is a significant burden to animal production in most areas of the world. Improving our knowledge of physiological and metabolic mechanisms of acclimation may contribute to the development of procedures that may help to maintain health and production efficiency under hot temperature. The effect of Ulmus pumila (UP) extract in inducing Heat Shock Proteins (HSPs) expression in heat-stressed RAW264.7 macrophage cells was investigated. Cell viability assay showed a dose dependent increase in cells after treatment with UP for 24 hours. RT-PCR and western blot analysis showed that increasing concentrations of UP induce the expression of Heat Shock Factor 1 (HSF1) and dose dependently upregulated the expression of Heat shock protein 70 (Hsp70) and Hsp90. LPS-induced nitric oxide was dose-dependently reduced while phagocytic activity greatly recovered with UP treatment. These data demonstrated that UP can be a potential candidate in the development of cytoprotective agent against heat stress.

• Proceedings of the Microbiological Society of Korea Conference
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• 2005.05a
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• pp.105-109
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• 2005

Heat Shock Transcription Factor (HSF), and the promoter heat Shock Element (HSE), are among the most highly conserved transcriptional regulatory elements in nature. HSF mediates the transcriptional response of eukaryotic cells to heat, infection and inflammation, pharmacological agents, and other stresses. While HSF is essential for cell viability in yeast, oogenesis and early development in Drosophila, extended life-span in C. elegans, and extra-embryonic development and stress resistance in mammals, little is known about its full range of biological target genes. We used whole genome analyses to identify virtually all of the direct transcriptional targets of yeast HSF, representing nearly three percent of the genomic loci. The majority of the identified loci are heat-inducibly bound by yeast HSF, and the target genes encode proteins that have a broad range of biological functions including protein folding and degradation, energy generation, protein secretion, maintenance of cell integrity, small molecule transport, cell signaling, and transcription. Approximately 30% of the HSF direct target genes are also induced by the diauxic shift, in which glucose levels begin to be depleted. We demonstrate that phosphorylation of HSF by Snf1 kinase is responsible for expression of a subset of HSF targets upon glucose starvation.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.3
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• pp.419-427
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• 2016

There is a high association of heat shock on the alteration of energy and lipid metabolism. The alterations associated with thermal stress are composed of gene expression changes and adaptation through biochemical responses. Previous study showed that Angelica gigas Nakai (AGN) root extract promoted adipogenic differentiation in murine 3T3-L1 preadipocytes under the normal temperature condition. However, its effect in heat shocked 3T3-L1 cells has not been established. In this study, we investigated the effect of AGN root hot water extract in the adipogenic differentiation of murine 3T3-L1 preadipocytes following heat shock and its possible mechanism of action. Thermal stress procedure was executed within the same stage of preadipocyte confluence (G0) through incubation at $42^{\circ}C$ for one hour and then allowed to recover at normal incubation temperature of $37^{\circ}C$ for another hour before AGN treatment for both cell viability assay and Oil Red O. Cell viability assay showed that AGN was able to dose dependently (0 to $400{\mu}g/mL$) increase cell proliferation under normal incubation temperature and also was able to prevent cytotoxicity due to heat shock accompanied by cell proliferation. Confluent preadipocytes were subjected into heat shock procedure, recovery and then AGN treatment prior to stimulation with the differentiation solution. Heat shocked preadipocytes exhibited reduced differentiation as supported by decreased amount of lipid accumulation in Oil Red O staining and triglyceride measurement. However, those heat shocked preadipocytes that then were given AGN extract showed a dose dependent increase in lipid accumulation as shown by both evaluation procedures. In line with these results, real-time polymerase chain reaction (RT-PCR) and Western blot analysis showed that AGN increased adipogenic differentiation by upregulating heat shock protection related genes and proteins together with the adipogenic markers. These findings imply the potential of AGN in heat shock amelioration among 3T3-L1 preadipocytes through heat shock factor and proteins augmentation and enhanced adipogenic marker expression.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.457-465
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• 2018

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

• Biomedical Science Letters
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• v.9 no.2
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• pp.59-65
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• 2003

When cells are exposed to proteotoxic stresses such as heat shock, amino acid analogs, and heavy metals, they increase the synthesis of the heat shock proteins (HSPs) by activating the heat shock transcription factor 1 (HSF1), whose activity is controlled via multiple steps including homotrimerization, nuclear translocation, DNA binding, and hyperphosphorylation. Under unstressed conditions, the HSF1 activity is repressed through its constitutive phosphorylation by glycogen synthase kinase 3$\beta$ (GSK3$\beta$), extracellular regulated kinase 1/2 (ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). However, the protein kinase (s) responsible for HSF1 hyperphosphorylation and activation is not yet identified. In the present study, we observed that profile of p38 mitogen-activated protein kinase (p38MAPK) activation in response to heat shock was very similar to those of HSF1 hyperphosphorylation and nuclear translocation. Therefore, we investigated whether p38MAPK is involved in the heat shock-induced HSF1 activation and HSP expression. Here we show that the p38MAPK inhibitors, SB202190 and SB203580, but not other inhibitors including the MEK1/2 inhibitor PD98059 and the PI3-K inhibitor LY294002 and wortmannin, suppress HSF1 hyperphosphorylation in response to heat shock and L-azetidine 2-carboxylic acid (Azc), but not to heavy metals. Furthermore, heat shock-induced HSF1-DNA binding and HSP72 expression was specifically prevented by the p38MAPK inhibitors, but not by the MEK1/2 inhibitor and the PI3-K inhibitors. These results suggest that SB202190- and SB203580-sensitive p38MAPK may positively regulate HSP gene regulation in response to heat shock and amino acid analogs.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1041-1048
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• 2018

Purpose: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. Materials and Methods: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. Results: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). Conclusion: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

• Bulletin of the Korean Chemical Society
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• v.20 no.6
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• pp.636-638
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• 1999

• BMB Reports
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• v.42 no.1
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• pp.16-21
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• 2009

Three novel Class A genes that encode heat shock transcription factor (HSF) were cloned from Oryza Sativa L using a yeast hybrid method. The OsHSF7 gene was found to be rapidly expressed in high levels in response to temperature, which indicates that it may be involved in heat stress reception and response. Over-expression of OsHSF7 in transgenic Arabidopsis could not induced over the expression of most target heat stress-inducible genes of HSFs; however, the transcription of some HSF target genes was more abundant in transgenic plants following two hours of heat stress treatment. In addition, those transgenic plants also had a higher basal thermotolerance, but not acquired thermotolerance. Collectively, the results of this study indicate that OsHSF7 might play an important role in the response to high temperature. Specifically, these findings indicate that OsHSF7 may be useful in the production of transgenic monocots that can over-express protective genes such as HSPs in response to heat stress, which will enable such plants to tolerate high temperatures.