Changes in Gene Expression After Brief Ischemic Insults as Potential Mediators of Induced Tolerance: Postischemic Temperature as a Variable Affecting the Stress Response

Author(s):  
S. Suga ◽  
T. S. Nowak
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Elisa T. S. de Carvalho ◽  
Marco A. Cordeiro ◽  
Luana S. Rodrigues ◽  
Daniela Ortolani ◽  
Regina C. Spadari

AbstractThe stress response is adaptive and aims to guarantee survival. However, the persistence of a stressor can culminate in pathology. Catecholamines released as part of the stress response over activate beta adrenoceptors (β-AR) in the heart. Whether and how stress affects the expression of components of the intracellular environment in the heart is still, however, unknown. This paper used microarray to analyze the gene expression in the left ventricle wall of rats submitted to foot shock stress, treated or not treated with the selective β2-AR antagonist ICI118,551 (ICI), compared to those of non-stressed rats also treated or not with ICI, respectively. The main findings were that stress induces changes in gene expression in the heart and that β2-AR plays a role in this process. The vast majority of genes disregulated by stress were exclusive for only one of the comparisons, indicating that, in the same stressful situation, the profile of gene expression in the heart is substantially different when the β2-AR is active or when it is blocked. Stress induced alterations in the expression of such a large number of genes seems to be part of stress-induced adaptive mechanism.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 605
Author(s):  
Jana Jandova ◽  
Anh B. Hua ◽  
Jocelyn Fimbres ◽  
Georg T. Wondrak

There are two stable isotopes of hydrogen, protium (1H) and deuterium (2H; D). Cellular stress response dysregulation in cancer represents both a major pathological driving force and a promising therapeutic target, but the molecular consequences and potential therapeutic impact of deuterium (2H)-stress on cancer cells remain largely unexplored. We have examined the anti-proliferative and apoptogenic effects of deuterium oxide (D2O; ‘heavy water’) together with stress response gene expression profiling in panels of malignant melanoma (A375V600E, A375NRAS, G361, LOX-IMVI), and pancreatic ductal adenocarcinoma (PANC-1, Capan-2, or MIA PaCa-2) cells with inclusion of human diploid Hs27 skin fibroblasts. Moreover, we have examined the efficacy of D2O-based pharmacological intervention in murine models of human melanoma tumor growth and metastasis. D2O-induction of apoptosis was substantiated by AV-PI flow cytometry, immunodetection of PARP-1, and pro-caspase 3 cleavage, and rescue by pan-caspase inhibition. Differential array analysis revealed early modulation of stress response gene expression in both A375 melanoma and PANC-1 adenocarcinoma cells elicited by D2O (90%; ≤6 h) (upregulated: CDKN1A, DDIT3, EGR1, GADD45A, HMOX1, NFKBIA, or SOD2 (up to 9-fold; p < 0.01)) confirmed by independent RT-qPCR analysis. Immunoblot analysis revealed rapid onset of D2O-induced stress response phospho-protein activation (p-ERK, p-JNK, p-eIF2α, or p-H2AX) or attenuation (p-AKT). Feasibility of D2O-based chemotherapeutic intervention (drinking water (30% w/w)) was demonstrated in a severe combined immunodeficiency (SCID) mouse melanoma metastasis model using luciferase-expressing A375-Luc2 cells. Lung tumor burden (visualized by bioluminescence imaging) was attenuated by D2O, and inhibition of invasiveness was also confirmed in an in vitro Matrigel transwell invasion assay. D2O supplementation also suppressed tumor growth in a murine xenograft model of human melanoma, and median survival was significantly increased without causing adverse effects. These data demonstrate for the first time that systemic D2O administration impairs growth and metastasis of malignant melanoma through the pharmacological induction of deuterium (2H)-stress.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Maria Buerstmayr ◽  
Christian Wagner ◽  
Tetyana Nosenko ◽  
Jimmy Omony ◽  
Barbara Steiner ◽  
...  

Abstract Background Fusarium head blight (FHB) is a devastating disease of wheat worldwide. Resistance to FHB is quantitatively controlled by the combined effects of many small to medium effect QTL. Flowering traits, especially the extent of extruded anthers, are strongly associated with FHB resistance. Results To characterize the genetic basis of FHB resistance, we generated and analyzed phenotypic and gene expression data on the response to Fusarium graminearum (Fg) infection in 96 European winter wheat genotypes, including several lines containing introgressions from the highly resistant Asian cultivar Sumai3. The 96 lines represented a broad range in FHB resistance and were assigned to sub-groups based on their phenotypic FHB severity score. Comparative analyses were conducted to connect sub-group-specific expression profiles in response to Fg infection with FHB resistance level. Collectively, over 12,300 wheat genes were Fusarium responsive. The core set of genes induced in response to Fg was common across different resistance groups, indicating that the activation of basal defense response mechanisms was largely independent of the resistance level of the wheat line. Fg-induced genes tended to have higher expression levels in more susceptible genotypes. Compared to the more susceptible non-Sumai3 lines, the Sumai3-derivatives demonstrated higher constitutive expression of genes associated with cell wall and plant-type secondary cell wall biogenesis and higher constitutive and Fg-induced expression of genes involved in terpene metabolism. Gene expression analysis of the FHB QTL Qfhs.ifa-5A identified a constitutively expressed gene encoding a stress response NST1-like protein (TraesCS5A01G211300LC) as a candidate gene for FHB resistance. NST1 genes are key regulators of secondary cell wall biosynthesis in anther endothecium cells. Whether the stress response NST1-like gene affects anther extrusion, thereby affecting FHB resistance, needs further investigation. Conclusion Induced and preexisting cell wall components and terpene metabolites contribute to resistance and limit fungal colonization early on. In contrast, excessive gene expression directs plant defense response towards programmed cell death which favors necrotrophic growth of the Fg pathogen and could thus lead to increased fungal colonization.


2005 ◽  
Vol 52 (3,4) ◽  
pp. 137-144 ◽  
Author(s):  
Kazuhito Rokutan ◽  
Kyoko Morita ◽  
Kiyoshi Masuda ◽  
Kumiko Tominaga ◽  
Michiyo Shikishima ◽  
...  

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 558 ◽  
Author(s):  
Fukuan Du ◽  
Gangchun Xu ◽  
Zhijuan Nie ◽  
Pao Xu ◽  
Ruobo Gu

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0124564 ◽  
Author(s):  
David Behringer ◽  
Heike Zimmermann ◽  
Birgit Ziegenhagen ◽  
Sascha Liepelt

2020 ◽  
Author(s):  
Nadia M. V. Sampaio ◽  
Caroline M. Blassick ◽  
Jean-Baptiste Lugagne ◽  
Mary J. Dunlop

AbstractCell-to-cell heterogeneity in gene expression and growth can have critical functional consequences, such as determining whether individual bacteria survive or die following stress. Although phenotypic variability is well documented, the dynamics that underlie it are often unknown. This information is critical because dramatically different outcomes can arise from gradual versus rapid changes in expression and growth. Using single-cell time-lapse microscopy, we measured the temporal expression of a suite of stress response reporters in Escherichia coli, while simultaneously monitoring growth rate. In conditions without stress, we found widespread examples of pulsatile expression. Single-cell growth rates were often anti-correlated with gene expression, with changes in growth preceding changes in expression. These pulsatile dynamics have functional consequences, which we demonstrate by measuring survival after challenging cells with the antibiotic ciprofloxacin. Our results suggest that pulsatile expression and growth dynamics are common in stress response networks and can have direct consequences for survival.


2019 ◽  
Author(s):  
Carly D. Kenkel ◽  
Veronique J.L. Mocellin ◽  
Line K. Bay

AbstractThe mechanisms resulting in the breakdown of the coral symbiosis once the process of bleaching has been initiated remain unclear. Distinguishing symbiont loss from the abiotic stress response may shed light on the cellular and molecular pathways involved in each process. This study examined physiological changes and global gene expression patterns associated with white patch syndrome (WPS) in P. lobata, which manifests in localized bleaching independent of thermal stress. In addition, a meta-analysis of global gene expression studies in other corals and anemones was used to contrast differential regulation as a result of abiotic stress from expression patterns correlated with symbiotic state. Symbiont density, chlorophyll a content, holobiont productivity, instant calcification rate, and total host protein content were uniformly reduced in WPS relative to healthy tissue. While expression patterns associated with WPS were secondary to fixed effects of source colony, specific functional enrichments suggest that the viral infection putatively giving rise to this condition affects symbiont rather than host cells. The meta-analysis revealed that expression patterns in WPS-affected tissues were significantly correlated with prior studies examining short-term thermal stress responses. This correlation was independent of symbiotic state, as the strongest correlations were found between WPS adults and both symbiotic adult and aposymbiotic coral larvae experiencing thermal stress, suggesting that the majority of expression changes reflect a non-specific stress response. Across studies, the magnitude and direction of expression change among particular functional enrichments suggests unique responses to stressor duration, and highlights unique responses to bleaching in an anemone model which engages in a non-obligate symbiosis.


2021 ◽  
Author(s):  
Georg T. Wondrak ◽  
Jana Jandova ◽  
Spencer J. Williams ◽  
Dominik Schenten

The germicidal properties of short wavelength ultraviolet C (UVC) light are well established and used to inactivate many viruses and other microbes. However, much less is known about germicidal effects of terrestrial solar UV light, confined exclusively to wavelengths in the UVA and UVB regions. Here, we have explored the sensitivity of the human coronaviruses HCoV-NL63 and SARS-CoV-2 to solar-simulated full spectrum ultraviolet light (sUV) delivered at environmentally relevant doses. First, HCoV-NL63 coronavirus inactivation by sUV-exposure was confirmed employing (i) viral plaque assays, (ii) RT-qPCR detection of viral genome replication, and (iii) infection-induced stress response gene expression array analysis. Next, a detailed dose-response relationship of SARS-CoV-2 coronavirus inactivation by sUV was elucidated, suggesting a half maximal suppression of viral infectivity at low sUV doses. Likewise, extended sUV exposure of SARS-CoV-2 blocked cellular infection as revealed by plaque assay and stress response gene expression array analysis. Moreover, comparative (HCoV-NL63 versus SARS-CoV-2) single gene expression analysis by RT-qPCR confirmed that sUV exposure blocks coronavirus-induced redox, inflammatory, and proteotoxic stress responses. Based on our findings, we estimate that solar ground level full spectrum UV light impairs coronavirus infectivity at environmentally relevant doses. Given the urgency and global scale of the unfolding SARS-CoV-2 pandemic, these prototype data suggest feasibility of solar UV-induced viral inactivation, an observation deserving further molecular exploration in more relevant exposure models.


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