Role played by BRCA1 in regulating the cellular response to stress

2001 ◽  
Vol 31 (1) ◽  
pp. 257 ◽  
Author(s):  
P.M. Gilmore ◽  
J.E. Quinn ◽  
P.B. Mullan ◽  
H.N. Andrews ◽  
N. McCabe ◽  
...  
Keyword(s):  
Cellular Response ◽  
Response To Stress

scholarly journals Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Adelaida M Celaya ◽  
Isabel Sánchez-Pérez ◽  
Jose M Bermúdez-Muñoz ◽  
Lourdes Rodríguez-de la Rosa ◽  
Laura Pintado-Berninches ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cellular Response ◽  
Redox Status ◽  
Mitogen Activated Protein Kinase ◽  
Progressive Hearing Loss ◽  
Knock Out ◽  
Auditory Evoked Responses ◽  
Mitogen Activated Protein ◽  
Response To Stress ◽  
Stress Signals

Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1–/– mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1–/– mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.

Role played by BRCA1 in regulating the cellular response to stress

2003 ◽  
Vol 31 (1) ◽  
pp. 257-262 ◽  
Author(s):  
P.M. Gilmore ◽  
J.E. Quinn ◽  
P.B. Mullan ◽  
H.N. Andrews ◽  
N. McCabe ◽  
...  
Keyword(s):  
Cellular Response ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Breast Cancer Susceptibility Gene ◽  
Dna Breaks ◽  
Double Strand Dna Breaks ◽  
Response To Stress

BRCA1 (breast-cancer susceptibility gene 1) is a tumour suppressor gene that is mutated in the germline of women with a genetic predisposition to breast and ovarian cancer. In this review, we examine the role played by BRCA1 in mediating the cellular response to stress. We review the role played by BRCA1 in detecting and signalling the presence of DNA damage, particularly double-strand DNA breaks, and look at the evidence to support a role for BRCA1 in regulating stress response pathways such as the c-Jun N-terminal kinase/stress-activated protein kinase pathway. In addition, we examine the role played by BRCA1 in mediating both cell-cycle arrest and apoptosis following different types of cellular insult, and how this may be modulated by the presence or absence of associated proteins such as p53. Finally, we explore the possibility that many of the functions associated with BRCA1 may be based on transcriptional regulation of key downstream genes that have been implicated in the regulation of these specific cellular pathways.

scholarly journals Identification of the C3a Receptor (C3AR1) as the Target of the VGF-derived Peptide TLQP-21 in Rodent Cells

2013 ◽  
Vol 288 (38) ◽  
pp. 27434-27443 ◽  
Author(s):  
Sebastien Hannedouche ◽  
Valerie Beck ◽  
Juliet Leighton-Davies ◽  
Martin Beibel ◽  
Guglielmo Roma ◽  
...  
Keyword(s):  
G Protein ◽  
Cellular Response ◽  
G Protein Coupled Receptors ◽  
Proteolytic Processing ◽  
Rodent Models ◽  
Cellular Functions ◽  
Genome Wide ◽  
Response To Stress ◽  
G Protein Coupled ◽  
Human Receptor

TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing, has been shown to modulate energy metabolism, differentiation, and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described. This study describes the use of a series of studies that show G protein-coupled receptor-mediated biological activity of TLQP-21 signaling in CHO-K1 cells. Unbiased genome-wide sequencing of the transcriptome from responsive CHO-K1 cells identified a prioritized list of possible G protein-coupled receptors bringing about this activity. Further experiments using a series of defined receptor antagonists and siRNAs led to the identification of complement C3a receptor-1 (C3AR1) as a target for TLQP-21 in rodents. We have not been able to demonstrate so far that this finding is translatable to the human receptor. Our results are in line with a large number of physiological observations in rodent models of food intake and metabolic control, where TLQP-21 shows activity. In addition, the sensitivity of TLQP-21 signaling to pertussis toxin is consistent with the known signaling pathway of C3AR1. The binding of TLQP-21 to C3AR1 not only has effects on signaling but also modulates cellular functions, as TLQP-21 was shown to have a role in directing migration of mouse RAW264.7 cells.

scholarly journals Effects of diethyldithiocarbamate and endogenous polyamine content on cellular responses to hydrogen peroxide cytotoxicity

1989 ◽  
Vol 260 (2) ◽  
pp. 487-490 ◽  
Author(s):  
P M Harari ◽  
M E Tome ◽  
D J M Fuller ◽  
S W Carper ◽  
E W Gerner
Keyword(s):  
Heat Shock ◽  
Cellular Response ◽  
Chinese Hamster ◽  
Resting Cells ◽  
H2o2 Treatment ◽  
Polyamine Content ◽  
Response To Stress ◽  
Stress Dependent ◽  
Common Facet ◽  
Stimulation Of

In exponential-phase Chinese-hamster cells, 0.1 mM-diethyldithiocarbamate (DDC) afforded greater than 1 log survival protection to cultures treated before and during exposure to 1 mM-H2O2. Both DDC and H2O2 treatment stimulated the activity of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, within 4 h of exposure. DDC, and to a lesser degree H2O2, also stimulated the activity of spermidine N1-acetyltransferase (SAT), the rate-limiting enzyme in polyamine catabolism. The increase in SAT activity, after exposure to DDC or another stress (heat shock), was inhibited in cells depleted of putrescine and spermidine by alpha-difluoromethylornithine (DFMO), the enzyme-activated suicide inhibitor of ODC. Pretreatment with DFMO or heat shock also induced resistance to H2O2 cytotoxicity. Since SAT activity is low in resting cells, yet stimulation of enzyme activity depends on endogenous spermidine pools, these results suggest that the expression of SAT activity occurs by a mechanism involving a stress-dependent displacement of spermidine into a new intracellular compartment. The stimulation of ODC and SAT activities does not appear to be a necessary component of the mechanism by which DDC protects cells from H2O2 cytotoxicity, although spermidine displacement may be a common facet of the cellular response to stress.

scholarly journals Expression profiling indicating low selenium-sensitive microRNA levels linked to cell cycle and cell stress response pathways in the CaCo-2 cell line

2017 ◽  
Vol 117 (9) ◽  
pp. 1212-1221 ◽  
Author(s):  
Mark J. McCann ◽  
Kunjana Rotjanapun ◽  
John E. Hesketh ◽  
Nicole C. Roy
Keyword(s):  
Cell Cycle ◽  
Stress Response ◽  
Cell Line ◽  
Cellular Response ◽  
Biological Pathways ◽  
Response To Stress ◽  
Low Selenium ◽  
Cell Stress Response ◽  
Canonical Wnt ◽  
Cellular Dysfunction

AbstractSe is an essential micronutrient for human health, and fluctuations in Se levels and the potential cellular dysfunction associated with it may increase the risk for disease. Although Se has been shown to influence several biological pathways important in health, little is known about the effect of Se on the expression of microRNA (miRNA) molecules regulating these pathways. To explore the potential role of Se-sensitive miRNA in regulating pathways linked with colon cancer, we profiled the expression of 800 miRNA in the CaCo-2 human adenocarcinoma cell line in response to a low-Se (72 h at <40 nm) environment using nCounter direct quantification. These data were then examined using a range ofin silicodatabases to identify experimentally validated miRNA–mRNA interactions and the biological pathways involved. We identified ten Se-sensitive miRNA (hsa-miR-93-5p, hsa-miR-106a-5p, hsa-miR-205-5p, hsa-miR-200c-3p, hsa-miR-99b-5p, hsa-miR-302d-3p, hsa-miR-373-3p, hsa-miR-483-3p, hsa-miR-512-5p and hsa-miR-4454), which regulate 3588 mRNA in key pathways such as the cell cycle, the cellular response to stress, and the canonical Wnt/β-catenin, p53 and ERK/MAPK signalling pathways. Our data show that the effects of low Se on biological pathways may, in part, be due to these ten Se-sensitive miRNA. Dysregulation of the cell cycle and of the stress response pathways due to low Se may influence key genes involved in carcinogenesis.

scholarly journals Autophagy: molecular machinery, regulation, and implications for renal pathophysiology

2009 ◽  
Vol 297 (2) ◽  
pp. F244-F256 ◽  
Author(s):  
Sudharsan Periyasamy-Thandavan ◽  
Man Jiang ◽  
Patricia Schoenlein ◽  
Zheng Dong
Keyword(s):  
Mammalian Cells ◽  
Cellular Response ◽  
Nutrient Deprivation ◽  
Experimental Conditions ◽  
Induce Cell Death ◽  
The Core ◽  
Molecular Machinery ◽  
Response To Stress ◽  
Membrane Bound ◽  
And Function

Autophagy is a cellular process of “self-eating.” During autophagy, a portion of cytoplasm is enveloped in double membrane-bound structures called autophagosomes, which undergo maturation and fusion with lysosomes for degradation. At the core of the molecular machinery of autophagy is a specific family of genes or proteins called Atg. Originally identified in yeast, Atg orthologs are now being discovered in mammalian cells and have been shown to play critical roles in autophagy. Traditionally, autophagy is recognized as a cellular response to nutrient deprivation or starvation whereby cells digest cytoplasmic organelles and macromolecules to recycle nutrients for self-support. However, studies during the last few years have indicated that autophagy is a general cellular response to stress. Interestingly, depending on experimental conditions, especially stress levels, autophagy can directly induce cell death or act as a mechanism of cell survival. In this review, we discuss the molecular machinery, regulation, and function of autophagy. In addition, we analyze the recent findings of autophagy in renal systems and its possible role in renal pathophysiology.

scholarly journals The Highlighted Roles of Metabolic and Cellular Response to Stress Pathways Engaged in Circulating hsa-miR-494-3p and hsa-miR-661 in Alzheimer’s Disease

2021 ◽  
Vol 25 (1) ◽  
pp. 62-67
Author(s):  
Zohreh Hojati ◽  
Farzaneh Omidi ◽  
Moein Dehbashi ◽  
Bahram Mohammad Soltani ◽  
◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cellular Response ◽  
Response To Stress

scholarly journals Gene network analyses support subfunctionalization hypothesis for duplicated hsp70 genes in the Antarctic clam

2020 ◽  
Vol 25 (6) ◽  
pp. 1111-1116 ◽  
Author(s):  
Abigail Ramsøe ◽  
Melody S. Clark ◽  
Victoria A. Sleight
Keyword(s):  
Ribosomal Proteins ◽  
Cellular Response ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Heat Stress Response ◽  
Network Analyses ◽  
Genes Encoding ◽  
Response To Stress ◽  
The Antarctic

Abstract A computationally predicted gene regulatory network (GRN), generated from mantle-specific gene expression profiles in the Antarctic clam Laternula elliptica, was interrogated to test the regulation and interaction of duplicated inducible hsp70 paralogues. hsp70A and hsp70B were identified in the GRN with each paralogue falling into unique submodules that were linked together by a single shared second neighbour. Annotations associated with the clusters in each submodule suggested that hsp70A primarily shares regulatory relationships with genes encoding ribosomal proteins, where it may have a role in protecting the ribosome under stress. hsp70B, on the other hand, interacted with a suite of genes involved in signalling pathways, including four transcription factors, cellular response to stress and the cytoskeleton. Given the contrasting submodules and associated annotations of the two hsp70 paralogues, the GRN analysis suggests that each gene is carrying out additional separate functions, as well as being involved in the traditional chaperone heat stress response, and therefore supports the hypothesis that subfunctionalization has occurred after gene duplication. The GRN was specifically produced from experiments investigating biomineralization; however, this study shows the utility of such data for investigating multiple questions concerning gene duplications, interactions and putative functions in a non-model species.

scholarly journals Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal

2009 ◽  
Vol 424 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Bradford G. Hill ◽  
Brian P. Dranka ◽  
Luyun Zou ◽  
John C. Chatham ◽  
Victor M. Darley-Usmar
Keyword(s):  
Cell Death ◽  
Cellular Response ◽  
Protein Modification ◽  
Ventricular Myocytes ◽  
Critical Role ◽  
Reserve Capacity ◽  
Energy Demands ◽  
Lipid Species ◽  
Cellular Context ◽  
Response To Stress

Mitochondria play a critical role in mediating the cellular response to oxidants formed during acute and chronic cardiac dysfunction. It is widely assumed that, as cells are subjected to stress, mitochondria are capable of drawing upon a ‘reserve capacity’ which is available to serve the increased energy demands for maintenance of organ function, cellular repair or detoxification of reactive species. This hypothesis further implies that impairment or depletion of this putative reserve capacity ultimately leads to excessive protein damage and cell death. However, it has been difficult to fully evaluate this hypothesis since much of our information about the response of the mitochondrion to oxidative stress derives from studies on mitochondria isolated from their cellular context. Therefore the goal of the present study was to determine whether ‘bioenergetic reserve capacity’ does indeed exist in the intact myocyte and whether it is utilized in response to stress induced by the pathologically relevant reactive lipid species HNE (4-hydroxynonenal). We found that intact rat neonatal ventricular myocytes exhibit a substantial bioenergetic reserve capacity under basal conditions; however, on exposure to pathologically relevant concentrations of HNE, oxygen consumption was increased until this reserve capacity was depleted. Exhaustion of the reserve capacity by HNE treatment resulted in inhibition of respiration concomitant with protein modification and cell death. These data suggest that oxidized lipids could contribute to myocyte injury by decreasing the bioenergetic reserve capacity. Furthermore, these studies demonstrate the utility of measuring the bioenergetic reserve capacity for assessing or predicting the response of cells to stress.

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