scholarly journals Role of heat shock factor-1 activation in the doxorubicin-induced heart failure in mice

2010 ◽  
Vol 298 (6) ◽  
pp. H1832-H1841 ◽  
Author(s):  
Kaushik Vedam ◽  
Yoshinori Nishijima ◽  
Lawrence J. Druhan ◽  
Mahmood Khan ◽  
Nicanor I. Moldovan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Heat Shock ◽  
Mrna Level ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Knock Out ◽  
Apoptotic Protein ◽  
Shock Proteins

Treating cancer patients with chemotherapeutics, such as doxorubicin (Dox), cause dilated cardiomyopathy and congestive heart failure because of oxidative stress. On the other hand, heat shock factor-1 (HSF-1), a transcription factor for heat shock proteins (Hsps), is also known to be activated in response to oxidative stress. However, the possible role of HSF-1 activation and the resultant Hsp25 in chemotherapeutic-induced heart failure has not been investigated. Using HSF-1 wild-type (HSF-1+/+) and knock-out (HSF-1−/−) mice, we tested the hypothesis that activation of HSF-1 plays a role in the development of Dox-induced heart failure. Higher levels of Hsp25 and its phosphorylated forms were found in the failing hearts of Dox-treated HSF-1+/+ mice. More than twofold increase in Hsp25 mRNA level was found in Dox-treated hearts. Proteomic analysis showed that there is accumulation and aggregation of Hsp25 in Dox-treated failing hearts. Additionally, Hsp25 was found to coimmunoprecipitate with p53 and vice versa. Further studies indicated that the Dox-induced higher levels of Hsp25 transactivated p53 leading to higher levels of the pro-apoptotic protein Bax, but other p53-related proteins remained unaltered. Moreover, HSF-1−/− mice showed significantly reduced Dox-induced heart failure and higher survival rate, and there was no change in Bax upon treating with Dox in HSF-1−/− mice. From these results we propose a novel mechanism for Dox-induced heart failure: increased expression of Hsp25 because of oxidant-induced activation of HSF-1 transactivates p53 to increase Bax levels, which leads to heart failure.

The possible role of heat shock factor-1 in the negative regulation of heme oxygenase-1

2005 ◽  
Vol 37 (3) ◽  
pp. 604-615 ◽  
Author(s):  
Yenn-Hwei Chou ◽  
Feng-Ming Ho ◽  
Der-Zen Liu ◽  
Shyr-Yi Lin ◽  
Li-Hsueh Tsai ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heme Oxygenase ◽  
Heat Shock Factor ◽  
Negative Regulation ◽  
Heme Oxygenase 1 ◽  
Heat Shock Factor 1

scholarly journals AKT1 mediates multiple phosphorylation events that functionally promote HSF1 activation

2020 ◽  
Author(s):  
Wen-Cheng Lu ◽  
Ramsey Omari ◽  
Haimanti Ray ◽  
Richard L. Carpenter
Keyword(s):  
Heat Shock ◽  
Functional Role ◽  
Transcriptional Activity ◽  
Heat Shock Factor 1 ◽  
Heat Stress Response ◽  
Subsequent Investigation ◽  
Important Regulator ◽  
Shock Proteins ◽  
Hsf1 Gene

AbstractThe heat stress response activates the transcription factor heat shock factor 1 (HSF1), which subsequently upregulates heat shock proteins to maintain the integrity of the proteome. HSF1 activity requires nuclear localization, trimerization, DNA binding, phosphorylation, and gene transactivation. Phosphorylation at S326 is an important regulator of HSF1 transcriptional activity. Phosphorylation at S326 is mediated by AKT1, mTOR, p38, and MEK1. mTOR, p38, and MEK1 all phosphorylated S326 but AKT1 was the more potent activator. Mass spectrometry showed that AKT1 phosphorylated HSF1 at T142, S230, and T527 in addition to S326 whereas the other kinases did not. Subsequent investigation revealed that phosphorylation at T142 is necessary for HSF1 trimerization and that S230, S326, and T527 are required for HSF1 gene transactivation and recruitment of TFIIB and CDK9. This study suggests that HSF1 activity is regulated by phosphorylation at specific residues that promote different stages of HSF1 activation. Furthermore, this is the first study to identify the functional role of these phosphorylation events.

Role of Heat Shock Factor 1 in HIV

2020 ◽  
Author(s):  
Xinfeng Xu ◽  
Xiaoyan Pan ◽  
Shuwen Liu
Keyword(s):  
Heat Shock ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1

scholarly journals Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Earl G. Noble ◽  
Garry X. Shen
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Inflammatory Mediators ◽  
Metabolic Disorders ◽  
Cell Injury ◽  
Vascular Inflammation ◽  
Atherosclerotic Cardiovascular Disease ◽  
Heat Shock Factor 1 ◽  
Shock Proteins

Heat shock proteins (Hsp) play critical roles in the body’s self-defense under a variety of stresses, including heat shock, oxidative stress, radiation, and wounds, through the regulation of folding and functions of relevant cellular proteins. Exercise increases the levels of Hsp through elevated temperature, hormones, calcium fluxes, reactive oxygen species (ROS), or mechanical deformation of tissues. Isotonic contractions and endurance- type activities tend to increase Hsp60 and Hsp70. Eccentric muscle contractions lead to phosphorylation and translocation of Hsp25/27. Exercise-induced transient increases of Hsp inhibit the generation of inflammatory mediators and vascular inflammation. Metabolic disorders (hyperglycemia and dyslipidemia) are associated with type 1 diabetes (an autoimmune disease), type 2 diabetes (the common type of diabetes usually associated with obesity), and atherosclerotic cardiovascular disease. Metabolic disorders activate HSF/Hsp pathway, which was associated with oxidative stress, increased generation of inflammatory mediators, vascular inflammation, and cell injury. Knock down of heat shock factor-1 (HSF1) reduced the activation of key inflammatory mediators in vascular cells. Accumulating lines of evidence suggest that the activation of HSF/Hsp induced by exercise or metabolic disorders may play a dual role in inflammation. The benefits of exercise on inflammation and metabolism depend on the type, intensity, and duration of physical activity.

scholarly journals HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

2019 ◽  
Vol 20 (22) ◽  
pp. 5815 ◽  
Author(s):  
Kovács ◽  
Sigmond ◽  
Hotzi ◽  
Bohár ◽  
Fazekas ◽  
...  
Keyword(s):  
Heat Shock ◽  
High Throughput ◽  
Ribosome Biogenesis ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Genes Encoding ◽  
Shock Proteins

: HSF1 (heat shock factor 1) is an evolutionarily conserved master transcriptional regulator of the heat shock response (HSR) in eukaryotic cells. In response to high temperatures, HSF1 upregulates genes encoding molecular chaperones, also called heat shock proteins, which assist the refolding or degradation of damaged intracellular proteins. Accumulating evidence reveals however that HSF1 participates in several other physiological and pathological processes such as differentiation, immune response, and multidrug resistance, as well as in ageing, neurodegenerative demise, and cancer. To address how HSF1 controls these processes one should systematically analyze its target genes. Here we present a novel database called HSF1Base (hsf1base.org) that contains a nearly comprehensive list of HSF1 target genes identified so far. The list was obtained by manually curating publications on individual HSF1 targets and analyzing relevant high throughput transcriptomic and chromatin immunoprecipitation data derived from the literature and the Yeastract database. To support the biological relevance of HSF1 targets identified by high throughput methods, we performed an enrichment analysis of (potential) HSF1 targets across different tissues/cell types and organisms. We found that general HSF1 functions (targets are expressed in all tissues/cell types) are mostly related to cellular proteostasis. Furthermore, HSF1 targets that are conserved across various animal taxa operate mostly in cellular stress pathways (e.g., autophagy), chromatin remodeling, ribosome biogenesis, and ageing. Together, these data highlight diverse roles for HSF1, expanding far beyond the HSR.

scholarly journals The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

2016 ◽  
Vol 21 (5) ◽  
pp. 745-753 ◽  
Author(s):  
Philip L. Hooper ◽  
Heather D. Durham ◽  
Zsolt Török ◽  
Paul L. Hooper ◽  
Tim Crul ◽  
...  
Keyword(s):  
Heat Shock ◽  
Memory Consolidation ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1
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