scholarly journals The Heat Shock Response in the Western Honey Bee (Apis mellifera) is Antiviral

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 245 ◽  
Author(s):  
Alexander J. McMenamin ◽  
Katie F. Daughenbaugh ◽  
Michelle L. Flenniken
Keyword(s):  
Apis Mellifera ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Honey Bee ◽  
Heat Shock Response ◽  
Honey Bees ◽  
Immune Gene ◽  
Protein Encoding ◽  
Shock Response

Honey bees (Apis mellifera) are an agriculturally important pollinator species that live in easily managed social groups (i.e., colonies). Unfortunately, annual losses of honey bee colonies in many parts of the world have reached unsustainable levels. Multiple abiotic and biotic stressors, including viruses, are associated with individual honey bee and colony mortality. Honey bees have evolved several antiviral defense mechanisms including conserved immune pathways (e.g., Toll, Imd, JAK/STAT) and dsRNA-triggered responses including RNA interference and a non-sequence specific dsRNA-mediated response. In addition, transcriptome analyses of virus-infected honey bees implicate an antiviral role of stress response pathways, including the heat shock response. Herein, we demonstrate that the heat shock response is antiviral in honey bees. Specifically, heat-shocked honey bees (i.e., 42 °C for 4 h) had reduced levels of the model virus, Sindbis-GFP, compared with bees maintained at a constant temperature. Virus-infection and/or heat shock resulted in differential expression of six heat shock protein encoding genes and three immune genes, many of which are positively correlated. The heat shock protein encoding and immune gene transcriptional responses observed in virus-infected bees were not completely recapitulated by administration of double stranded RNA (dsRNA), a virus-associated molecular pattern, indicating that additional virus–host interactions are involved in triggering antiviral stress response pathways.

Inhibition of Interleukin-6 Signaling with CNTO328 Sensitizes Multiple Myeloma Cells to Bortezomib and Attenuates Proteasome Inhibitor-Mediated Induction of the Anti-Apoptotic Heat Shock Protein Response.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1574-1574
Author(s):  
Peter M. Voorhees ◽  
Deborah J. Kuhn ◽  
George W. Small ◽  
John S. Strader ◽  
Robert Corringham ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Proteasome Inhibitor ◽  
Myeloma Cell ◽  
Significant Advance ◽  
Hsp 70 ◽  
Shock Response

Abstract The proteasome inhibitor bortezomib represents a significant advance in the treatment of multiple myeloma, but its efficacy is limited by a number of resistance mechanisms. One of the most important is the heat shock protein (HSP) and stress response pathways which, through members such as HSP-70 and mitogen-activated protein kinase (MAPK) phosphatase (MKP)-1, oppose the pro-apoptotic activities of bortezomib. Because interleukin (IL)-6 signaling augments the heat shock response through signal transducer and activator of transcription (STAT)-1 and heat shock transcription factor (HSF)-1, we hypothesized that downregulation of IL-6 signaling would attenuate HSP induction by bortezomib, thereby enhancing its anti-myeloma activity. Treatment of the IL-6-dependent multiple myeloma cell lines KAS-6 and ANBL-6 with the combination of bortezomib and CNTO328, a chimeric monoclonal IL-6 neutralizing antibody, resulted in greater reduction of cell viability than with either drug alone in a time- and concentration-dependent manner. This was associated with an enhanced induction of apoptosis which, under some conditions, was greater than the sum of the two individual agents alone, suggesting a synergistic interaction. Similar findings were not seen when using isotype control antibodies, and in studies of the IL-6-independent RPMI 8226 myeloma cell line. Increased activity was seen when cells were pre-treated with CNTO328 followed by bortezomib, or when they were treated with both agents concurrently, compared to treatment with bortezomib followed by CNTO328. Treatment with CNTO328 potently inhibited IL-6-mediated downstream signaling pathways, as demonstrated by marked blockade of STAT-3 and p44/42 MAPK phosphorylation. Enhanced activity of the combination regimen correlated with attenuated induction by bortezomib of the heat shock and stress response proteins HSP-70 and MKP-1 by up to 45% and 90%, respectively. Notably, CNTO328 markedly reduced levels of transcriptionally active phospho-STAT-1 and hyperphosphorylated HSF-1. Other strategies to suppress the heat shock response, including the use of the pharmacologic inhibitor KNK437, also yielded evidence for a synergistic anti-myeloma effect in combination with bortezomib. The synergistic activity of KNK437 and bortezomib was reproduced in normal mouse embryo fibroblasts (MEFs), but blunted in HSF-1 knockout MEFs. Taken together, the above data demonstrate that inhibition of IL-6 signaling enhances the anti-myeloma activity of bortezomib. They also support the hypothesis that this occurs, at least in part, by attenuating proteasome inhibitor-mediated induction of the heat shock response through downregulation of transcriptionally active STAT-1 and HSF-1. These findings provide a strong rationale for future translation of the CNTO328/bortezomib combination into the clinic.

C-terminal heat shock protein 90 modulators produce desirable oncogenic properties

2015 ◽  
Vol 13 (16) ◽  
pp. 4627-4631 ◽  
Author(s):  
Y. Wang ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Cellular Protection ◽  
Protection Mechanism ◽  
C Terminus ◽  
N Terminus ◽  
Shock Response

The cellular protection mechanism, the heat shock response, is only activated by classical heat shock 90 inhibitors (Hsp90) that “target” the N-terminus of the protein, but not by those that modulate the C-terminus.

scholarly journals Induction of Heat Shock Protein 70 in Mouse RPE as an In Vivo Model of Transpupillary Thermal Stimulation

2020 ◽  
Vol 21 (6) ◽  
pp. 2063
Author(s):  
Mooud Amirkavei ◽  
Marja Pitkänen ◽  
Ossi Kaikkonen ◽  
Kai Kaarniranta ◽  
Helder André ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
In Vivo Model ◽  
Tunel Staining ◽  
Long Duration ◽  
Shock Response

The induction of heat shock response in the macula has been proposed as a useful therapeutic strategy for retinal neurodegenerative diseases by promoting proteostasis and enhancing protective chaperone mechanisms. We applied transpupillary 1064 nm long-duration laser heating to the mouse (C57Bl/6J) fundus to examine the heat shock response in vivo. The intensity and spatial distribution of heat shock protein (HSP) 70 expression along with the concomitant probability for damage were measured 24 h after laser irradiation in the mouse retinal pigment epithelium (RPE) as a function of laser power. Our results show that the range of heating powers for producing heat shock response while avoiding damage in the mouse RPE is narrow. At powers of 64 and 70 mW, HSP70 immunostaining indicates 90 and 100% probability for clearly elevated HSP expression while the corresponding probability for damage is 20 and 33%, respectively. Tunel staining identified the apoptotic regions, and the estimated 50% damaging threshold probability for the heating (ED50) was ~72 mW. The staining with Bestrophin1 (BEST1) demonstrated RPE cell atrophy with the most intense powers. Consequently, fundus heating with a long-duration laser provides an approachable method to develop heat shock-based therapies for the RPE of retinal disease model mice.

Induction of the heat shock response in Arabidopsis by heat shock protein 70 inhibitor VER-155008

2019 ◽  
Vol 46 (10) ◽  
pp. 925
Author(s):  
Erina Matsuoka ◽  
Naoki Kato ◽  
Masakazu Hara
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Wheat Germ ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Wheat Germ Extract ◽  
Chlorophyll Contents ◽  
Shock Response ◽  
Human Hsp70

The heat shock protein 90 (HSP90) inhibitor, geldanamycin, is a chemical inducer of the heat shock response (HSR) in Arabidopsis. Geldanamycin is thought to activate the heat shock signal by dissociating the HSP90-heat shock factor (HSF) complex. Recent studies have indicated that plant HSP70 is also associated with HSF, suggesting that inhibition of HSP70 may induce the HSR. However, no studies have been conducted to test this hypothesis. Here, we found that a specific HSP70 inhibitor VER-155008 activated the promoter of a small HSP gene (At1 g53540, HSP17.6C-CI) of Arabidopsis, which was shown to be activated by geldanamycin and other HSP90 inhibitors. The production of HSP17.6C-CI, HSP70 and HSP90.1 proteins in Arabidopsis was enhanced by the addition of VER-155008. The reduction of chlorophyll contents by heat shock was ameliorated by VER-155008. Chaperone analyses indicated that VER-155008 inhibited the chaperone activities of wheat germ extract and human HSP70/HSP40, respectively. These results suggest that the inhibition of HSP70 by VER-155008 enhanced the heat tolerance of Arabidopsis by inducing the HSR in the plant.

scholarly journals Molecular Basis of the Defective Heat Stress Response in Mycobacterium leprae

2007 ◽  
Vol 189 (24) ◽  
pp. 8818-8827 ◽  
Author(s):  
Diana L. Williams ◽  
Tana L. Pittman ◽  
Mike Deshotel ◽  
Sandra Oby-Robinson ◽  
Issar Smith ◽  
...  
Keyword(s):  
Heat Stress ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Elevated Temperatures ◽  
Transcriptional Response ◽  
Mycobacterium Leprae ◽  
Heat Stress Response ◽  
Regulatory Circuits ◽  
Shock Response

ABSTRACT Mycobacterium leprae, a major human pathogen, grows poorly at 37°C. The basis for its inability to survive at elevated temperatures was investigated. We determined that M. leprae lacks a protective heat shock response as a result of the lack of transcriptional induction of the alternative sigma factor genes sigE and sigB and the major heat shock operons, HSP70 and HSP60, even though heat shock promoters and regulatory circuits for these genes appear to be intact. M. leprae sigE was found to be capable of complementing the defective heat shock response of mycobacterial sigE knockout mutants only in the presence of a functional mycobacterial sigH, which orchestrates the mycobacterial heat shock response. Since the sigH of M. leprae is a pseudogene, these data support the conclusion that a key aspect of the defective heat shock response in M. leprae is the absence of a functional sigH. In addition, 68% of the genes induced during heat shock in M. tuberculosis were shown to be either absent from the M. leprae genome or were present as pseudogenes. Among these is the hsp/acr2 gene, whose product is essential for M. tuberculosis survival during heat shock. Taken together, these results suggest that the reduced ability of M. leprae to survive at elevated temperatures results from the lack of a functional transcriptional response to heat shock and the absence of a full repertoire of heat stress response genes, including sigH.

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