Over-expressed heat shock protein 70 protects cells against DNA damage caused by ultraviolet C in a dose-dependent manner

2005 ◽  
Author(s):  
Tangchun Wu ◽  
Piye Niu ◽  
Lin Liu ◽  
Zhiyong Gong ◽  
Hao Tan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Dependent Manner ◽  
Ultraviolet C ◽  
Dose Dependent

scholarly journals Overexpressed heat shock protein 70 protects cells against DNA damage caused by ultraviolet C in a dose-dependent manner

2006 ◽  
Vol 11 (2) ◽  
pp. 162 ◽  
Author(s):  
Piye Niu ◽  
Lin Liu ◽  
Zhiyong Gong ◽  
Hao Tan ◽  
Feng Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Dependent Manner ◽  
Ultraviolet C ◽  
Dose Dependent

scholarly journals The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wonkyoung Cho ◽  
Xiongjie Jin ◽  
Junfeng Pang ◽  
Yan Wang ◽  
Nahid F. Mivechi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Cell Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Delineating the mechanisms that drive hepatic injury and hepatocellular carcinoma (HCC) progression is critical for development of novel treatments for recurrent and advanced HCC but also for the development of diagnostic and preventive strategies. Heat shock protein 70 (HSP70) acts in concert with several cochaperones and nucleotide exchange factors and plays an essential role in protein quality control that increases survival by protecting cells against environmental stressors. Specifically, the HSP70-mediated response has been implicated in the pathogenesis of cancer, but the specific mechanisms by which HSP70 may support malignant cell transformation remains to be fully elucidated. Here, we show that genetic ablation of HSP70 markedly impairs HCC initiation and progression by distinct but overlapping pathways. This includes the potentiation of the carcinogen-induced DNA damage response, at the tumor initiation stage, to increase the p53-dependent surveillance response leading to the cell cycle exit or death of genomically damaged differentiated pericentral hepatocytes, and this may also prevent their conversion into more proliferating HCC progenitor cells. Subsequently, activation of a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) negative feedback pathway diminishes oncogenic signals, thereby attenuating premalignant cell transformation and tumor progression. Modulation of HSP70 function may be a strategy for interfering with oncogenic signals driving liver cell transformation and tumor progression, thus providing an opportunity for human cancer control.

scholarly journals Expression and therapeutic relevance of heat-shock protein 90 in pancreatic endocrine tumors

2011 ◽  
Vol 19 (3) ◽  
pp. 217-232 ◽  
Author(s):  
Philipp Mayer ◽  
Andreas Harjung ◽  
Marco Breinig ◽  
Lars Fischer ◽  
Volker Ehemann ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Line ◽  
Therapeutic Effects ◽  
Endocrine Tumors ◽  
Human Pancreas ◽  
Dependent Manner ◽  
Hsp90 Inhibitors ◽  
Pancreatic Endocrine Tumors ◽  
Dose Dependent

Pancreatic endocrine tumors (PET) represent a heterogenous group of neoplasms. Although surgical resection is considered a safe and effective treatment for many PET, therapeutic options for inoperable and progressive PET are limited. The expression of heat-shock protein (HSP) 90 was investigated in 120 clinically and pathomorphologically well-characterized PET from 84 patients using immunohistochemistry. In addition, in 19 snap–frozen PET and in three healthy pancreatic tissues, we performed immunoblot analyses, and in 15 snap–frozen PET and in three healthy pancreatic tissues, we investigated the expression of HSP90 isoforms by means of semiquantitative RT-PCR. Functional tests were conducted using the human pancreas carcinoid cell line BON and the mouse insulinoma cell line β-TC-3. HSP90 was expressed in 95% of the PET patients. The transcript levels of the HSP90 isoforms HSP90α, HSP90β, glucose-related protein 94, and TNF receptor-associated protein 1 were significantly increased in PET compared with non-neoplastic pancreatic tissues. The treatment of the cell lines BON and β-TC-3 with the HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin resulted in significant, dose-dependent reduction of cell viability, cell cycle arrest, and increased apoptosis. Furthermore, HSP90 inhibition induced the degradation and inactivation of several oncogenetic HSP90 client proteins in a time- and dose-dependent manner. HSP90 inhibitors increased the therapeutic effects of doxorubicin and 5-fluorucacil in BON and β-TC-3 cells. HSP90 is expressed in the vast majority of PET and its inhibition reveals significant treatment effects in vitro. Thus, HSP90 qualifies as a promising new target.

Involvement of heat shock protein-70 in the mechanism of hydrogen peroxide-induced DNA damage: The role of lysosomes and iron

2007 ◽  
Vol 42 (4) ◽  
pp. 567-577 ◽  
Author(s):  
P DOULIAS ◽  
P KOTOGLOU ◽  
M TENOPOULOU ◽  
D KERAMISANOU ◽  
T TZAVARAS ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70

scholarly journals Chicken Heat Shock Protein 90 Is a Component of the Putative Cellular Receptor Complex of Infectious Bursal Disease Virus

2007 ◽  
Vol 81 (16) ◽  
pp. 8730-8741 ◽  
Author(s):  
Ta-Wei Lin ◽  
Chi-Wen Lo ◽  
Su-Yuan Lai ◽  
Ruey-Jane Fan ◽  
Chao-Jung Lo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Infectious Bursal Disease Virus ◽  
Heat Shock Protein 90 ◽  
Infectious Bursal Disease ◽  
Cellular Receptor ◽  
Dependent Manner ◽  
Receptor Complex ◽  
Bursal Disease ◽  
Dose Dependent

ABSTRACT Infectious bursal disease virus (IBDV) causes a highly contagious disease in young chicks and leads to significant economic losses in the poultry industry. The capsid protein VP2 of IBDV plays an important role in virus binding and cell recognition. VP2 forms a subviral particle (SVP) with immunogenicity similar to that of the IBDV capsid. In the present study, we first showed that SVP could inhibit IBDV infection to an IBDV-susceptible cell line, DF-1 cells, in a dose-dependent manner. Second, the localizations of the SVP on the surface of DF-1 cells were confirmed by fluorescence microscopy, and the specific binding of the SVP to DF-1 cells occurred in a dose-dependent manner. Furthermore, the attachment of SVP to DF-1 cells was inhibited by an SVP-induced neutralizing monoclonal antibody against IBDV but not by denatured-VP2-induced polyclonal antibodies. Third, the cellular factors in DF-1 cells involved in the attachment of SVP were purified by affinity chromatography using SVP bound on the immobilized Ni2+ ions. A dominant factor was identified as being chicken heat shock protein 90 (Hsp90) (cHsp90) by mass spectrometry. Results of biotinylation experiments and indirect fluorescence assays indicated that cHsp90 is located on the surface of DF-1 cells. Virus overlay protein binding assays and far-Western assays also concluded that cHsp90 interacts with IBDV and SVP, respectively. Finally, both Hsp90 and anti-Hsp90 can inhibit the infection of DF-1 cells by IBDV. Taken together, for the first time, our results suggest that cHsp90 is part of the putative cellular receptor complex essential for IBDV entry into DF-1 cells.

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