Soluble Guanylate Cyclase Signalling Mediates Etoposide Resistance in Progressing Small Cell Lung Cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB47088 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR6539070_1.fastq.gz | Fastqsanger.gz | |||
| ERR6539070_2.fastq.gz | Fastqsanger.gz | |||
| ERR6539080_1.fastq.gz | Fastqsanger.gz | |||
| ERR6539080_2.fastq.gz | Fastqsanger.gz | |||
| ERR6539090_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 132 |
Similar Datasets
Project description:Total RNA were extracted from Guanylate Cyclase Soluble Subunit Beta-3 (GUCY1B3) overexpression U87 MG stable cell lines and U87 MG cells. Three RNA samples of each of the two cell lines were used for microarray analysis to compare gene expression profile Guanylate Cyclase Soluble Subunit Beta-3 (GUCY1B3) was cloned into pCDNA3.1D/V5-His-TOPO plasmid (Invitrgen) and then transfected into U87 MG (ATCC HTB-1) cells to generate stable overexpression cells. RNA from the stable cell lines and U87 MG were used for microarray
2016-06-15 | E-GEOD-83344 | biostudies-arrayexpress
Project description:Total RNA were extracted from Guanylate Cyclase Soluble Subunit Beta-3 (GUCY1B3) overexpression U87 MG stable cell lines and U87 MG cells. Three RNA samples of each of the two cell lines were used for microarray analysis to compare gene expression profile
2016-06-15 | GSE83344 | GEO
Project description:We studied the role of the soluble guanylate cyclase CYG12 in the response of Chlamydomonas reinhardtii to anoxia and darkness. To gain insights into potentially disturbed signaling pathways resulting in different responses of the transcriptome, we performed an RNA-sequencing study to obtain transcriptome profiles of the C. reinhardtii wild-type and a CYG12 knockdown strain in aerobiosis and anaerobiosis in darkness compared to normoxia in the light
2017-11-22 | GSE98442 | GEO
Project description:Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC. The emergence of acquired resistance to standard platinum-etoposide chemotherapy in small cell lung cancer (SCLC) is a common event. Here, the authors using paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models reveal a mechanism of drug resistance in SCLC mediated by Notch and nitric oxide activation of soluble guanylate cyclase signalling.
| S-EPMC8599617 | biostudies-literature
Project description:Diabetic kidney disease (DKD) is the most common cause of renal failure. Therapeutics development is hampered by our incomplete understanding of animal models on a cellular level. We show that ZSF1 rats recapitulate human DKD on a phenotypic and transcriptomic level. Tensor decomposition prioritizes proximal tubule (PT) and stroma as phenotype-relevant cell types exhibiting a continuous lineage relationship. As DKD features endothelial dysfunction, oxidative stress, and nitric oxide depletion, soluble guanylate cyclase (sGC) is a promising DKD drug target. sGC expression is specifically enriched in PT and stroma. In ZSF1 rats, pharmacological sGC activation confers considerable benefits over stimulation and is mechanistically related to improved oxidative stress regulation, resulting in enhanced downstream cGMP effects. Finally, we define sGC gene co-expression modules, which allow stratification of human kidney samples by DKD prevalence and disease-relevant measures such as kidney function, proteinuria, and fibrosis, underscoring the relevance of the sGC pathway to patients.
2023-02-24 | GSE209821 | GEO
Project description:Stone1996 - activation of soluble guanylate
cyclase by nitric oxide
This features the two step binding of
NO to soluble Guanylyl Cyclase as proposed by
Stone
JR, Marletta MA. Biochemistry (1996) 35(4):1093-9 . There is a
fast step binding scheme and a slow step binding scheme. The
difference lies in the binding of a NO to a non-heme site on sGC,
which may not necessarily be the same site of binding during the
initial binding. The rates have been directly used models.
This model is described in the article:
Spectral and kinetic studies
on the activation of soluble guanylate cyclase by nitric
oxide.
Stone JR, Marletta MA.
Biochemistry 1996 Jan; 35(4):
1093-1099
Abstract:
The soluble form of guanylate cyclase (sGC) is the only
definitive receptor for the signaling agent nitric oxide (.NO).
The enzyme is a heterodimer of homologous subunits in which
each subunit binds 1 equiv of 5-coordinate high-spin heme. .NO
increases the Vmax of sGC up to 400-fold and has previously
been shown to bind to the heme to form a 5-coordinate complex.
Using stopped-flow spectrophotometry, it is demonstrated that
the binding of .NO to the heme of sGC is a complex process. .NO
first binds to the heme to form a 6-coordinate nitrosyl
complex, which then converts to a 5-coordinate nitrosyl complex
through one of two ways. For 28 +/- 4% of the heme, the
6-coordinate nitrosyl complex rapidly (approximately 20 s-1)
converts to the 5-coordinate complex. For the remaining 72 +/-
4% of the heme, the conversion of the 6-coordinate nitrosyl
complex to a 5-coordinate nitrosyl complex is slow (0.1-1.0
s-1) and is dependent upon the interaction of .NO with an
unidentified non-heme site on the protein. The heme (200 nM)
was completely converted to the 5-coordinate state with as
little as 500 nM .NO, and the equilibrium dissociation constant
of .NO for activating the enzyme was determined to be < or =
250 nM. Gel-filtration analysis indicates that the binding of
.NO to the heme has no effect on the native molecular mass of
the protein. Correlation of electronic absorption spectra with
activity measurements indicates that the 5-coordinate nitrosyl
form of the enzyme is activated relative to the resting
5-coordinate ferrous form of the enzyme.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000198.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000198 | BioModels
Project description:Treatment effects of soluble guanylate cyclase modulation on diabetic kidney disease at single-cell resolution
| PRJNA862532 | ENA
Project description:The soluble guanylate cyclase stimulator praliciguat promotes ischemic leg reperfusion in leptin receptor-deficient mice
| PRJNA899452 | ENA
Project description:We exploited six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. WES data from the patient germ line and from the biopsy of the solid tumour is reported in this submission and RNASeq data from these models is reported previously (E-MTAB-8465 - RNA of Small Cell Lung Cancer Circulating Tumour Cells Derived Explants). Both chemo naive and progression models were taken from patients and their drug sensitivity tested within the mouse models. Blood samples were taken from patients, and RosetteSep CTC Enrichment was used to implant these cells into mice. Tumours were allowed to grow, then extracted and re-implanted into second and third generations of mice, before finally being subjected to molecular profiling.
2021-09-15 | E-MTAB-10880 | biostudies-arrayexpress
Project description:Background: Moyamoya is a cerebrovascular condition of unknown mechanism characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the compensatory development of abnormal “moyamoya” vessels. It leads to ischemic and hemorrhagic stroke. We describe a novel autosomal recessive disease leading to severe moyamoya and early onset achalasia and report its cause in 3 unrelated families. Methods: We used a combination of genetic linkage and exome sequencing in 2 consanguineous to identify rare shared variants. Sanger sequencing of GUCY1A3, the sole gene mutated in both families, was then conducted in the third family. Platelets from one of the patients and controls were used to carry out functional studies. Results: Homozygous mutations of GUCY1A3 gene encoding the alpha1 subunit of soluble guanylate cyclase (sGC), the major receptor for Nitric Oxide (NO), were identified in all 3 families. Platelet analysis showed a complete loss of the mutated protein and showed an unexpected stimulatory role of sGC within platelets. Conclusion: The NO/sGC/cGMP pathway is a major pathway controlling vascular smooth muscle (VSMC) relaxation, vascular tone and vascular remodeling. Our data suggest that alterations of this pathway may lead to an abnormal vascular remodeling process in sensitive vascular areas with low blood
2014-06-19 | GSE48099 | GEO