scholarly journals HSPB1 Promotes Doxorubicin-induced Cardiomyocyte Pyroptosis by Inhibiting AATF

2021 ◽  
Author(s):  
Yao Tang ◽  
Yaxiu Liu ◽  
Shuang Fu ◽  
Xinbin Zheng ◽  
Mingrui Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Adverse Effects ◽  
Small Interfering Rna ◽  
Therapeutic Strategy ◽  
Caspase 3 ◽  
Shock Proteins ◽  
Interfering Rna ◽  
Novel Therapeutic

Abstract Background: Doxorubicin (DOX) has been widely used for the treatment of different kinds of cancers. However, the adverse effects, especially cardiotoxicity, which limit the long-term use of DOX. Although some signaling pathways have been investigated to be participated in DOX-induced cardiotoxicity, however, the mechanisms underlying DOX-induced cardiotoxicity need to be further investigated. Recent study suggested that heat shock proteins (HSPs) play a role in cell apoptosis and pyroptosis. However, we do not know yet whether heat shock protein beta-1 (HSPB1), a member of HSPs family, is involved in DOX-induced cardiomyocyte pyroptosis. This study aimed to evaluate the effects of HSPB1 and apoptosis antagonizing transcription factor (AATF) in DOX-induced pyroptosis in cardiomycytes.Results: We found that DOX remarkably enhanced the expression of HSPB1 but reduces AATF expression in cardiomyocytes. We also found that either inhibition of HSPB1 by small interfering RNA (siRNA) or overexpression of AATF by transfection of AATF plasmid significantly attenuated DOX-induced cardiomyocyte pyroptosis. Moreover, HSPB1 interacts with AATF. Furthermore, inhibition of HSPB1 and AATF restores the DOX-induced cardiomyocyte pyroptosis. Conclusion: Our findings reveal a novel pathway that cardiomyocyte pyroptosis is regulated through HSPB1-AATF-caspase-3-GSDME pathway following DOX treatment, suggesting that HSPB1-AATF-dependent pyroptosis may provide a novel therapeutic strategy to reduce cardiotoxicity induced by DOX.

scholarly journals Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases?

Immunology ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Manon A. A. Jansen ◽  
Rachel Spiering ◽  
Femke Broere ◽  
Jacob M. van Laar ◽  
John D. Isaacs ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Autoimmune Diseases ◽  
Therapeutic Strategy ◽  
Tolerogenic Dendritic Cells ◽  
Shock Proteins ◽  
Novel Therapeutic

Acetylcholinesterase (AChE) and heat shock proteins (Hsp70) of gypsy moth (Lymantria dispar L.) larvae in response to long-term fluoranthene exposure

Chemosphere ◽  
2016 ◽  
Vol 159 ◽  
pp. 565-569 ◽  
Author(s):  
Marija Mrdaković ◽  
Larisa Ilijin ◽  
Milena Vlahović ◽  
Dragana Matić ◽  
Anja Gavrilović ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Gypsy Moth ◽  
Lymantria Dispar ◽  
Shock Proteins

The CRZ-1 Transcription Factor Regulates Hsp 80 Involves in the Acquisition of Thermotolerance, and NCA-2 for Calcium Stress Tolerance in Neurospora Crassa

2021 ◽  
Author(s):  
Avishek Roy ◽  
Ranjan Tamuli
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Neurospora Crassa ◽  
Stress Condition ◽  
Stress Conditions ◽  
Start Codon ◽  
Expression Levels ◽  
Heat Shock Stress ◽  
Shock Proteins ◽  
Shock Stress

Abstract Heat shock proteins (Hsps) are molecular chaperones and required for survival of organisms under heat stress conditions. In this study, we studied Hsp80, a member of the Hsp90 family, in Neurospora crassa. The expression of hsp80 was severely reduced in the N. crassa calcineurin B subunit RIP-mutant (cnb-1RIP) strains under the heat shock conditions. Furthermore, the expression levels of cnb-1, hsp60, hsp80, and the calcineurin-regulated transcription factor crz-1 were increased, but expression levels were reduced in the presence of the calcineurin inhibitor FK506 under the heat shock stress in the N. crassa wild type. Therefore, the calcineurin-crz-1 signaling pathway transcriptionally regulates hsp60 and hsp80 under the heat shock stress condition in N. crassa. In addition, the transcript levels of trm-9 and nca-2, a Ca2+ sensor and a Ca2+ ATPase, respectively, were increased under the heat shock stress condition. Moreover, the expression of the hsp80, but not the hsp60, was reduced in the Δtrm-9, Δnca-2, and the Δtrm-9 Δnca-2 double mutants. These results suggested that hsp80, trm-9, and nca-2 play a role in coping the heat shock stress in N. crassa. We found that CRZ-1 binds to 5ʹ-CCTTCACA-3ʹ and 5ʹ-AGCGGAGC-3ʹ 8 bp nucleotide sequences, located about 1075 bp and 679 bp upstream of the ATG start codon, respectively, of hsp80. We also found that CRZ-1 binds to an 8 bp nucleotide sequence 5ʹ-ACCGCGCC-3ʹ, located 234 bp upstream of the ATG start codon of nca-2 under Ca2+ stress condition. Thus, cnb-1, hsp60, hsp80, and crz-1 are involved in the heat shock stress response in N. crassa. Moreover, CRZ-1 upregulates the expressions of hsp80 and nca-2 under the heat shock stress and Ca2+ stress conditions, respectively, in N. crassa.

scholarly journals Regulatory effect of heat shock transcription factor-1 gene on heat shock proteins and its transcriptional regulation analysis in small abalone Haliotis diversicolor

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Zhang ◽  
Yuting Li ◽  
Yulong Sun ◽  
Mingxing Guo ◽  
Jianjun Feng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Binding Site ◽  
Promoter Activity ◽  
Luciferase Activity ◽  
Haliotis Diversicolor ◽  
Shock Response ◽  
Flanking Region ◽  
Small Abalone ◽  
Shock Proteins

Abstract Background The effects of diverse stresses ultimately alter the structures and functions of proteins. As molecular chaperones, heat shock proteins (HSPs) are a group of highly conserved proteins that help in the refolding of misfolded proteins and the elimination of irreversibly damaged proteins. They are mediated by a family of transcription factors called heat shock factors (HSFs). The small abalone Haliotis diversicolor is a species naturally distributed along the southern coast of China. In this study, the expression of HdHSF1 was inhibited by RNAi in hemocytes in order to further elucidate the regulatory roles of HdHSF1 on heat shock responsive genes in abalone. Meanwhile, to understand the transcriptional regulation of the HdHSF1 gene, the 5′-upstream regulatory region of HdHSF1 was characterized, and the relative promoter activity was examined by dual-luciferase reporter gene assay system in HEK293T cell lines. Results After the inhibition of the H. diversicolor HSF1 gene (HdHSF1) by dsRNA (double-stranded RNA), the expression of most heat shock related-genes was down-regulated (p < 0.05). It indicated the importance of HdHSF1 in the heat shock response of H. diversicolor. Meanwhile, 5′-flanking region sequence (2633 bp) of the HdHSF1 gene was cloned; it contained a putative core promoter region, TATA box, CAAT box, CpG island, and many transcription elements. In HEK293T cells, the 5′-flanking region sequence can drive expression of the enhanced green fluorescent protein (EGFP), proving its promoter function. Exposure of cells to the high-temperature (39 °C and 42 °C) resulted in the activation of HdHSF1 promoter activity, which may explain why the expression of the HdHSF1 gene participates in heat shock response. Luciferase activity of different recombinant plasmids, which contained different truncated promoter fragments of the HdHSF1 gene in HEK293T cells, revealed the possible active regions of the promoter. To further identify the binding site of the critical transcription factor in the region, an expression vector with the site-directed mutation was constructed. After being mutated on the GATA-1 binding site, we found that the luciferase activity was significantly increased, which suggested that the GATA-1 binding site has a certain weakening effect on the activity of the HdHSF1 promoter. Conclusions These findings suggest that GATA-1 may be one of the transcription factors of HdHSF1, and a possible signaling pathway mediated by HdHSF1 may exist in H. diversicolor to counteract the adverse effects of heat shock stress.

scholarly journals Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5671 ◽  
Author(s):  
Hong-Yan Sui ◽  
Guang-Yu Zhao ◽  
Jian-Dong Huang ◽  
Dong-Yan Jin ◽  
Kwok-Yung Yuen ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Virus Replication ◽  
Small Interfering Rna ◽  
Influenza A ◽  
Rna Targeting ◽  
Interfering Rna

scholarly journals NF-κB signaling pathway is inhibited by heat shock independently of active transcription factor HSF1 and increased levels of inducible heat shock proteins

2011 ◽  
Vol 16 (12) ◽  
pp. 1168-1175 ◽  
Author(s):  
Patryk Janus ◽  
Małgorzata Pakuła-Cis ◽  
Magdalena Kalinowska-Herok ◽  
Natalia Kashchak ◽  
Katarzyna Szołtysek ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Signaling Pathway ◽  
Active Transcription ◽  
Shock Proteins
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