scholarly journals Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sina Kavalakatt ◽  
Abdelkrim Khadir ◽  
Dhanya Madhu ◽  
Heikki A. Koistinen ◽  
Fahd Al-Mulla ◽  
...  
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Er Stress ◽  
Glucose Uptake ◽  
Heat Shock Response ◽  
Cellular Stress Response ◽  
Mrna Levels ◽  
Obesity And Diabetes ◽  
Shock Response ◽  
Urocortin 3

AbstractThe neuropeptide urocortin 3 (UCN3) has a beneficial effect on metabolic disorders, such as obesity, diabetes, and cardiovascular disease. It has been reported that UCN3 regulates insulin secretion and is dysregulated with increasing severity of obesity and diabetes. However, its function in the adipose tissue is unclear. We investigated the overexpression of UCN3 in 3T3-L1 preadipocytes and differentiated adipocytes and its effects on heat shock response, ER stress, inflammatory markers, and glucose uptake in the presence of stress-inducing concentrations of palmitic acid (PA). UCN3 overexpression significantly downregulated heat shock proteins (HSP60, HSP72 and HSP90) and ER stress response markers (GRP78, PERK, ATF6, and IRE1α) and attenuated inflammation (TNFα) and apoptosis (CHOP). Moreover, enhanced glucose uptake was observed in both preadipocytes and mature adipocytes, which is associated with upregulated phosphorylation of AKT and ERK but reduced p-JNK. Moderate effects of UCN3 overexpression were also observed in the presence of 400 μM of PA, and macrophage conditioned medium dramatically decreased the UCN3 mRNA levels in differentiated 3T3-L1 cells. In conclusion, the beneficial effects of UCN3 in adipocytes are reflected, at least partially, by the improvement in cellular stress response and glucose uptake and attenuation of inflammation and apoptosis.

scholarly journals Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abdoulaye Diane ◽  
Naela Mahmoud ◽  
Ilham Bensmail ◽  
Namat Khattab ◽  
Hanan A. Abunada ◽  
...  
Keyword(s):  
Heat Shock ◽  
Er Stress ◽  
Glucose Uptake ◽  
Lipoic Acid ◽  
Heat Shock Response ◽  
Transcriptional Activation ◽  
Hepg2 Cells ◽  
Metabolic Stress ◽  
C2c12 Cells ◽  
Shock Response

AbstractPersistent ER stress, mitochondrial dysfunction and failure of the heat shock response (HSR) are fundamental hallmarks of insulin resistance (IR); one of the early core metabolic aberrations that leads to type 2 diabetes (T2D). The antioxidant α-lipoic acid (ALA) has been shown to attenuate metabolic stress and improve insulin sensitivity in part through activation of the heat shock response (HSR). However, these studies have been focused on a subset of heat shock proteins (HSPs). In the current investigation, we assessed whether ALA has an effect on modulating the expression of DNAJB3/HSP40 cochaperone; a potential therapeutic target with a novel role in mitigating metabolic stress and promoting insulin signaling. Treatment of C2C12 cells with 0.3 mM of ALA triggers a significant increase in the expression of DNAJB3 mRNA and protein. A similar increase in DNAJB3 mRNA was also observed in HepG2 cells. We next investigated the significance of such activation on endoplasmic reticulum (ER) stress and glucose uptake. ALA pre-treatment significantly reduced the expression of ER stress markers namely, GRP78, XBP1, sXBP1 and ATF4 in response to tunicamycin. In functional assays, ALA treatment abrogated significantly the tunicamycin-mediated transcriptional activation of ATF6 while it enhanced the insulin-stimulated glucose uptake and Glut4 translocation. Silencing the expression of DNAJB3 but not HSP72 abolished the protective effect of ALA on tunicamycin-induced ER stress, suggesting thus that DNAJB3 is a key mediator of ALA-alleviated tunicamycin-induced ER stress. Furthermore, the effect of ALA on insulin-stimulated glucose uptake is significantly reduced in C2C12 and HepG2 cells transfected with DNAJB3 siRNA. In summary, our results are supportive of an essential role of DNAJB3 as a molecular target through which ALA alleviates ER stress and improves glucose uptake.

scholarly journals Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3168
Author(s):  
Oleg Chen ◽  
Soňa Michlíková ◽  
Lisa Eckhardt ◽  
Marit Wondrak ◽  
Adriana M. De Mendoza ◽  
...  
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Cellular Stress Response ◽  
Proteotoxic Stress ◽  
Shock Response ◽  
Pre Treatment ◽  
Shock Proteins ◽  
The Impact

Hyperthermia (HT) combined with irradiation is a well-known concept to improve the curative potential of radiotherapy. Technological progress has opened new avenues for thermoradiotherapy, even for recurrent head and neck squamous cell carcinomas (HNSCC). Preclinical evaluation of the curative radiosensitizing potential of various HT regimens remains ethically, economically, and technically challenging. One key objective of our study was to refine an advanced 3-D assay setup for HT + RT research and treatment testing. For the first time, HT-induced radiosensitization was systematically examined in two differently radioresponsive HNSCC spheroid models using the unique in vitro “curative” analytical endpoint of spheroid control probability. We further investigated the cellular stress response mechanisms underlying the HT-related radiosensitization process with the aim to unravel the impact of HT-induced proteotoxic stress on the overall radioresponse. HT disrupted the proteome’s thermal stability, causing severe proteotoxic stress. It strongly enhanced radiation efficacy and affected paramount survival and stress response signaling networks. Transcriptomics, q-PCR, and western blotting data revealed that HT + RT co-treatment critically triggers the heat shock response (HSR). Pre-treatment with chemical chaperones intensified the radiosensitizing effect, thereby suppressing HT-induced Hsp27 expression. Our data suggest that HT-induced radiosensitization is adversely affected by the proteotoxic stress response. Hence, we propose the inhibition of particular heat shock proteins as a targeting strategy to improve the outcome of combinatorial HT + RT.

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.

scholarly journals Heat shock response relieves ER stress

2008 ◽  
Vol 27 (7) ◽  
pp. 1049-1059 ◽  
Author(s):  
Yu Liu ◽  
Amy Chang
Keyword(s):  
Heat Shock ◽  
Er Stress ◽  
Heat Shock Response ◽  
Shock Response

Heat shock response by EBV-immortalized B-lymphocytes from centenarians and control subjects: a model to study the relevance of stress response in longevity

2004 ◽  
Vol 39 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Marina Marini ◽  
Rosa Lapalombella ◽  
Silvia Canaider ◽  
Antonio Farina ◽  
Daniela Monti ◽  
...  
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
B Lymphocytes ◽  
Heat Shock Response ◽  
Control Subjects ◽  
Shock Response ◽  
And Control

Testing the hormetic nature of homeopathic interventions through stress response pathways

2010 ◽  
Vol 29 (7) ◽  
pp. 551-554 ◽  
Author(s):  
Suresh IS Rattan ◽  
Taru Deva
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Dose Response ◽  
Heat Shock Response ◽  
Unfolded Protein ◽  
Shock Response ◽  
Protein Response ◽  
Homeopathic Remedies ◽  
Homeopathic Drugs ◽  
Biphasic Dose Response

The scientific foundations of hormesis are now well established and include various biochemical and molecular criteria for testing the hormetic nature of chemicals and other modulators. In order to claim homeopathy as being hormetic, it is essential that, in addition to the hormetic biphasic dose response, homeopathic remedies should fulfill one or more molecular criteria. Since stress response pathways, such as heat shock response, antioxidative response, autophagic response and unfolded protein response, are integral components of the physiological hormesis, it is important that homeopathic drugs be tested for these pathways if these are to be considered as hormetins and to cause hormesis.

Analysis of RNA for transcripts for catalase and SP71 in rat hearts after in vivo hyperthermia

1991 ◽  
Vol 69 (5-6) ◽  
pp. 375-382 ◽  
Author(s):  
R. William Currie ◽  
Robert M. Tanguay
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Catalase Activity ◽  
Mrna Level ◽  
Regulation Of Transcription ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Control Heart ◽  
Shock Response ◽  
Human Hsp70

Hyperthermic stress induces synthesis of the major inducible (heat) stress protein (SP71) in all rat tissues. In addition, there is an increase in catalase activity in hearts at 24 and 48 h after the induction of the heat shock response. To more precisely define some of the molecular aspects of the induction of the heat shock response in hearts, we examined mRNA levels for the catalase, SP71 and HSP27. RNA was isolated from control hearts and at various time periods (0–24 h) of recovery after brief hyperthermic treatment and was analyzed by Northern blot analysis using as probes cDNA sequences for rat liver catalase, human HSP70 (inducible), and human HSP27. There was no detectable change in mRNA for catalase after heat shock or during recovery. Hyperthermic stress has no apparent effect on the regulation of transcription of mRNA coding for catalase, indicating that the increase in catalase activity is either translationally or post-translationally regulated. The human HSP70 cDNA did not hybridize to control heart RNA, but did hybridize to SP71 transcripts at 0, 1.5, and 3 h post heat shock. The mRNA level for SP71 peaked at 1.5 h, was reduced at 3 h, and became almost undetectable at 6 h post heat shock. Similarly, the human HSP27 cDNA did not hybridize to control heart RNA, but did hybridize to transcripts for HSP27 at 0, 1.5, 3, and up to 15 h post heat shock. Maximal signal for HSP27 was at 3 h post heat shock and was sharply reduced at 6 h post heat shock. The accumulation of transcripts for SP71 and HSP27 after hyperthermic stress is rapid, and degradation of the transcripts is almost complete by 6 h post heat shock.Key words: heat shock proteins, hyperthermia, catalase, heart, RNA.

scholarly journals Systemic activation coordinates the heat shock response of the insulin/IGF-1 pathway in Caenorhabditis elegans

2017 ◽  
Author(s):  
Ronen B Kopito ◽  
Kathie Watkins ◽  
Erel Levine
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Cellular Response ◽  
Precise Control ◽  
Cellular Processes ◽  
Shock Response ◽  
Stressed Cells ◽  
Shock Proteins

Exposure to high temperatures has an adverse effect on cellular processes and results in activation of the cellular heat shock response (HSR), a highly conserved program of inducible genes to maintain protein homeostasis1. The insulin/IGF-1 signaling (IIS) pathway, which has diverse roles from metabolism to stress response and longevity, is activated as part of the HSR2–4. Recent evidence suggest that the IIS pathway is able to affect proteostasis non-autonomously5,6, yet it is not known if it is activated autonomously in stressed cells or systemically as part of an organismic program. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue DAF-16 functions as the major target of the IIS pathway7 and, together with the heat-shock factor HSF-1, induce the expression of small heat shock proteins in response to heat shock8–10,3. Here we use a novel microfluidic device that allows precise control of the spatiotemporal temperature profile to show that cellular activation of DAF-16 integrates local temperature sensation with systemic signals. We demonstrate that DAF-16 activation in head sensory neurons is essential for DAF-16 activation in other tissues, but show that no known thermosensory neuron is individually required. Our findings demonstrate that systemic and cell-autonomous aspects of stress response act together to facilitate a coordinated cellular response at the organismic level.

scholarly journals The effect of aging on the autophagic and heat shock response in human peripheral blood mononuclear cells

2018 ◽  
Vol 105 (3) ◽  
pp. 247-256 ◽  
Author(s):  
JJ McCormick ◽  
TA VanDusseldorp ◽  
CG Ulrich ◽  
RL Lanphere ◽  
K Dokladny ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Heat Shock Response ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Shock Response ◽  
Blood Mononuclear Cells

Autophagy is a lysosome degradation pathway through which damaged organelles and macromolecules are degraded within the cell. A decrease in activity of the autophagic process has been linked to several age-associated pathologies, including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction. Here, we examined the differences in the autophagic response using autophagy-inducer rapamycin (Rapa) in peripheral blood mononuclear cells (PBMCs) from young (21.8 ± 1.9 years) and old (64.0 ± 3.7 years) individuals. Furthermore, we tested the interplay between the heat shock response and autophagy systems. Our results showed a significant increase in LC3-II protein expression in response to Rapa treatment in young but not in old individuals. This was associated with a decreased response in MAP1LC3B mRNA levels, but not SQSTM1/p62. Furthermore, HSPA1A mRNA was upregulated only in young individuals, despite no differences in HSP70 protein expression. The combined findings suggest a suppressed autophagic response following Rapa treatment in older individuals.

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