Examination of the Role of miR-23a in the Development of Thermotolerance

2020 ◽  
Vol 20 (3) ◽  
pp. 194-201 ◽  
Author(s):  
Rabih Roufayel ◽  
Seifedine Kadry
Keyword(s):  
Heat Shock ◽  
Large Body ◽  
The Novel ◽  
Rt Pcr ◽  
Cytochrome C Release ◽  
Proteotoxic Stress ◽  
Cell Clones ◽  
Control Shrna ◽  
Apoptotic Pathways ◽  
Shock Proteins

Background: Thermotolerance is an acquired state of increased heat resistance that occurs following exposure to non-lethal proteotoxic stress. A large body of evidences implicates that molecular chaperon members belonging to the heat shock protein family could be acting as potential mediators of the thermotolerant state. Objective: Recent evidence has demonstrated heat shock proteins HSP90, HSP70 and HSP27 have inhibited heat-induced cell death by intervening at various steps in stressinduced apoptotic pathways. Previous studies have shown that HSP70 prevented heatinduced apoptosis by preventing the NOXA dependent decrease in MCL-1 levels leading to both BAX activation and cytochrome c release from mitochondria. We have also demonstrated that HSP70 expressing cells have enhanced levels of miR-23a prevent heat-induced increase in NOXA levels and suppress apoptosis. Methods: Stably transfected cell lines expressing either a control shRNA or a miR-23a targeting shRNA are quantified using both RT-PCR and semi-quantitative RT-PCR to determine the effect of different hyperthermic exposure treatment on miR-23a and Noxa mRNA expression levels. Results: This study shows that thermotolerant-induced pre-heat shock treatment is capable of increasing miR-23a levels. Furthermore, stable cell clones expressing a miR- 23a targeting shRNA having reduced miR-23a levels are incapable of developing a thermotolerance state, leading to apoptosis. Conclusion: These results demonstrate the novel finding that miR-23a is an important factor in the development of the thermotolerant state.

scholarly journals Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance

2011 ◽  
Vol 58 (7) ◽  
pp. 1072-1080 ◽  
Author(s):  
Almudena Santón ◽  
Mónica García-Cosío ◽  
Eva Cristóbal ◽  
Alejandro Pascual ◽  
Alfonso Muriel ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Hodgkin Lymphoma ◽  
Prognostic Significance ◽  
Classical Hodgkin Lymphoma ◽  
Apoptotic Pathways ◽  
Shock Proteins

scholarly journals Heat shock proteins and cancer: intracellular chaperones or extracellular signalling ligands?

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160524 ◽  
Author(s):  
Stuart K. Calderwood
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Tumour Cells ◽  
Future Studies ◽  
Proteotoxic Stress ◽  
Wide Range ◽  
Window Of Vulnerability ◽  
Shock Proteins ◽  
Extracellular Signalling ◽  
Key Questions

Heat shock proteins (HSPs) are found at elevated concentrations in tumour cells, and this increase reflects the proteotoxic stress experienced by the cells due to expanding levels of the mutated oncoproteins that drive tumorigenesis. The protection of oncogenic proteins by HSPs offers a window of vulnerability in tumour metabolism that has been exploited using Hsp90-targeting drugs. Such compounds have been shown to cause inhibition and degradation of a wide range of proteins essential for oncogenesis. Recently, Hsp90 has also been shown to be secreted by tumour cells and to interact in autocrine or paracrine manners with the surfaces of adjacent cells, leading to increased growth and metastasis. Future studies will address a number of key questions associated with these findings, including the relative importance of intracellular versus extracellular HSPs in tumorigenesis, as well as overcoming potential problems with normal tissue toxicity associated with Hsp90 drugs. Targeting individual members of HSP families and inactivating extracellular HSPs may be desirable future approaches that offer increased selectivity in targeting HSPs in cancer. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

scholarly journals INCREASED HSP25 DRIVES THE TRANSITION FROM PROTEASOME TO AUTOPHAGY-MEDIATED DEGRADATION UNDER PROTEOTOXIC STRESS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S98-S99
Author(s):  
Jessica L Scheirer ◽  
Karl Rodriguez
Keyword(s):  
Heat Shock ◽  
Protein Degradation ◽  
Protein Misfolding ◽  
Gene Activation ◽  
Small Heat Shock Protein ◽  
C Elegans ◽  
Proteotoxic Stress ◽  
Main Driver ◽  
Worm Model ◽  
Shock Proteins

Abstract Accumulation of protein aggregates are a common pathology in many neurodegenerative disorders. This accumulation may be due to a function decline in the protein homeostasis network known to occur during the aging process. Small heat shock proteins are a class of molecular chaperones that assist in protein folding and ameliorates the degradation activity of the proteasome and autolysosome thereby decreasing disease-associated aggregates. Prior work in rodents and C. elegans has shown expression levels of the small heat shock protein 25 (HSP25) correlates with maximum lifespan potential. Increased levels of HSP25 extends lifespan in a transgenic C. elegans model. This lifespan extension is dependent on skn-1 with evidence suggesting an enrichment in several skn-1-related pathways, such as lysosomal genes. Concomitantly, proteasome activity declines while autolysosome activity increases. This observation might suggest a switch from proteasome degradation to autophagy as the main driver of protein degradation in C. elegans in this transgenic model. To investigate if a reduction of proteasome function and elevated lysosomal gene activation during aging and under proteotoxic stress are modulated by HSP25 we have crossed our HSP25-transgenic worm with an aggregating and non-aggregating tau worm model. This work will elucidate a possible mechanism that explains the change in the protein degradation response pathways potentially modulated by HSP25 during increased protein misfolding.

scholarly journals Characterization of the groESL Operon inListeria monocytogenes: Utilization of Two Reporter Systems (gfp and hly) for Evaluating In Vivo Expression

2001 ◽  
Vol 69 (6) ◽  
pp. 3924-3932 ◽  
Author(s):  
Cormac G. M. Gahan ◽  
James O'Mahony ◽  
Colin Hill
Keyword(s):  
Heat Shock ◽  
Fluorescent Protein ◽  
Ethanol Stress ◽  
Rt Pcr ◽  
Gene Encoding ◽  
Intracellular Expression ◽  
Green Fluorescent ◽  
Shock Proteins ◽  
Transcriptional Fusions

ABSTRACT The ability of intracellular pathogens to sense and adapt to the hostile environment of the host is an important factor governing virulence. We have sequenced the operon encoding the major heat shock proteins GroES and GroEL in the gram-positive food-borne pathogenListeria monocytogenes. The operon has a conserved orientation in the order groES groEL. Upstream ofgroES and in the opposite orientation is a gene encoding a homologue of the Bacillus subtilis protein YdiL, while downstream of groEL is a gene encoding a putative bile hydrolase. We used both reverse transcriptase-PCR (RT-PCR) and transcriptional fusions to the UV-optimized Aequorea victoria green fluorescent protein (GFPUV) to analyze expression of groESL under various environmental stress conditions, including heat shock, ethanol stress, and acid shock, and during infection of J774 mouse macrophage cells. Strains harboring GFPUV transcriptional fusions to the promoter region ofgroESL demonstrated a significant increase in fluorescence following heat shock that was detected by both fluorimetry and fluorescence microscopy. Using both RT-PCR and GFP technology we detected expression of groESL following internalization by J774 cells. Increased intracellular expression of dnaK was also determined using RT-PCR. We have recently described a system which utilizes L. monocytogenes hemolysin as an in vivo reporter of gene expression within the host cell phagosome (C. G. M. Gahan and C. Hill, Mol. Microbiol. 36:498–507, 2000). In this study a strain was constructed in which hemolysin expression was placed under the control of the groESL promoter. In this strain hemolysin expression during infection also confirms transcription from the groESL promoter during J774 and murine infection, albeit at lower levels than the known virulence factorplcA.

scholarly journals The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160525 ◽  
Author(s):  
Chengkai Dai
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Misfolding ◽  
Heat Shock Factor 1 ◽  
Growth And Survival ◽  
Proteotoxic Stress ◽  
Shock Proteins ◽  
Misfolding Diseases

The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

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