Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative proteomics of Hsp90 inhibition in Leishmania mexicana

ABSTRACT: Using a combination of mass spectrometry-based quantitative proteomics, chemical and metabolic labelling, we provide the first protein-level evidence that the Hsp90 inhibition affects the expression of hundreds of proteins in Leishmania spp. Our study defines the Leishmania parasite’s response to Hsp90 inhibition at its global proteome and provides a rich resource for future studies on Leishmania biology and antileishmanial drug development.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Leishmania Mexicana

SUBMITTER: Kalesh Karunakaran

LAB HEAD: Karunakaran Kalesh

PROVIDER: PXD024764 | Pride | 2021-04-23

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	DMSO_D1.wiff	Wiff
	DMSO_D2.wiff	Wiff
	DMSO_D3.wiff	Wiff
	Tanespi_T1.wiff	Wiff
	Tanespi_T2.wiff	Wiff

Items per page:

1 - 5 of 8

Similar Datasets

Quantitative chemical proteomics of Leishmania mexicana

Project description:We report the first systematic study of the effect of Hsp90 inhibition on the global protein synthesis in Leishmania parasites using an integrated chemical biology approach. Heat shock protein 90 (Hsp90) is a conserved molecular chaperone responsible for the folding of newly synthesised proteins. It is regarded as a master regulator of protein homeostasis of the cell, and its inhibition has been proposed to affect functions of a large array of its client proteins. We showed that the Hsp90 inhibition affects synthesis of many Leishmania proteins, with important chaperones and virulence factors showing an overall increased relative expression whilst many ribosomal proteins showing a down-regulation. This study defines the Leishmania parasite’s response to Hsp90 inhibition at its nascent global protein synthesis and provides a rich resource for future studies on Leishmania biology and antileishmanial drug development.

2021-04-23 | PXD022708 | Pride

Druggable Serine Proteases of Leishmania by Activity‐Based Protein Profiling

Project description:Leishmaniasis are a group of diseases caused by parasitic protozoa of the genus Leishmania. Current treatments are limited by difficult administration, high cost, poor efficacy, toxicity, and growing resistance. New agents, with new mechanisms of action, are urgently needed to treat the disease. Although extensively studied in other organisms, serine proteases (SPs) have not been widely explored as antileishmanial drug targets. Herein we report for the first time an activity-based protein profiling (ABPP) strategy to investigate new therapeutic targets within the SPs of the Leishmania parasites. Active site directed fluorophosphonate probes (rhodamine and biotin‐conjugated) were used for the detection and identification of active Leishmania serine hydrolases (SHs). Significant differences were observed in the SHs expression levels throughout the Leishmania life cycle and between different Leishmania species. Using iTRAQ-labelling-based quantitative proteomic mass spectrometry, we identified two targetable SPs in Leishmania mexicana: carboxypeptidase LmxM.18.0450 and prolyl oligopeptidase LmxM.36.6750. Druggability was ascertained by selective inhibition using the commercial serine protease inhibitors chymostatin, lactocystin and ZPP, which represent templates for future anti-leishmanial drug discovery programs. Collectively, the use of ABPP method complements existing genetic methods for target identification and validation in Leishmania.

2022-07-04 | PXD033616 | Pride

Starvation-specific NSPs in Leishmania mexicana parasites by quantitative proteomics

Project description:Using a combination of BONCAT technique and iTRAQ 3-plex quantitative proteomics MS, we profiled the de novo protein synthesis in the starving L. mexicana parasites in a temporally resolved manner. This approach uniquely integrates the high specificity of the BONCAT technique for the NSPs with the high sensitivity and multiplexed quantitation capability of the iTRAQ quantitative proteomics MS. Proof-of-concept experiments identified over 250 starvation-specific NSPs in the parasite and quantified the relative changes in abundance of these proteins as a function of duration of starvation.

2019-12-04 | PXD015827 | Pride

Protein profiling of stress-activated breast cancer cell models

Project description:This study provides insights into the efficacy of beta-blockers as breast cancer therapeutics.Cell line models of basal-type and estrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and ADRβ2-mediated cell behaviour including migration, invasion, adhesion, and proliferation in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified response biomarkers and drug targets. Protein profiling revealed the upregulation of the pro-metastatic gene LYPD3 in norepinephrine treated MDA MB 468 cells. Histology confirmed selective LYPD3 expression in clinical primary and metastatic breast tumours. These findings demonstrate that basal-type cancer models show a more aggressive ADRβ2-activated phenotype in the resting and stimulated state, which is attenuated by ADRβ2 inhibition, and explain some of the previous studies that have cast doubt on the value of beta-blocker therapy in breast cancer. These findings suggest that propranolol should be clinically evaluated in patients with basal-type tumours expressing high levels of ADRβ2 and LYPD3.

2020-05-26 | PXD009488 | Pride

Quantitative SWATH-Based Proteomic Profiling of Urine for the Identification of Endometrial Cancer Biomarkers in Symptomatic Women

Project description:In this study, we carried out quantitative SWATH-MS-based proteomic profiling of urine acquired from a cohort of symptomatic women with and without endometrial cancer.

2023-05-10 | PXD038860 | Pride

Transcriptional analysis of wild-type Leishmania species between both stages using full-genome DNA microarrays

Project description:Transcriptional analyses of L. infantum promastigote compared to L. infantum intracellular amastigote, and L. major promastigote compared to L. major intracellular amastigote The full-genome DNA microarray includes one 70mer-oligonucleotide probe for each gene of L. infantum and for each gene of L.major LV39 Keywords: stage-specific comparison Leishmania infantum: Two-condition experiment, promastigote stage vs amastigote stage. Six biological replicates for each stage, independently grown and harvested. One replicate per array Leishmania major: Two-condition experiment, promastigote stage vs amastigote stage. Four biological replicates for each stage, independently grown and harvested. One replicate per array

2008-05-28 | E-GEOD-10407 | biostudies-arrayexpress

Shotgun proteomic profiling of intestinal mucosa of rainbow trout Oncorhynchus mykiss

Project description:The objective of this study was to identify and quantify proteomic profiles of intestine of rainbow trout (Oncorhynchus mykiss). Specific pathogen free rainbow trout (mean length 15 ± 1 cm) were maintained in recirculating de-chlorinated water at 19±1 °C. Prior to the experiment, fish were distributed between aquaria. The test groups were infected by immersion of Yersinia ruckeri CSF007-82 (biotype 1) and 7959-11 (biotype 2) strains. The control group was immersed similar with sterile broth medium. Fish were anaesthetized and sampled aseptically at different time points. Each intestine was washed three times with sterile phosphate-buffered saline containing a cocktail of mammalian protease inhibitors. Intestinal mucosa was scraped with a sterile large scalpel blade. Intestinal samples were snap-frozen in liquid nitrogen and stored at –80 °C.

2019-11-12 | PXD011087 | Pride

Shotgun proteomic profiling of spleen of rainbow trout Oncorhynchus mykiss

Project description:The objective of this study was to identify and quantify proteomic profiles of spleen of rainbow trout Oncorhynchus mykiss. Specific pathogen free rainbow trout (mean length 15 ± 1 cm) were maintained in recirculating de-chlorinated water at 19±1 °C. Prior to the experiment, fish were distributed between 9 aquaria, 18 fish per aquarium. The test groups were infected by immersion of Yersinia ruckeri strains: CSF007-82 (biotype 1) and 7959-11 (biotype 2). The control group was immersed similar with sterile broth medium. There were 3 aquaria per each group (CSF007-82-infected, 7959-11-infected and control). Nine fish from infected and control fish groups were anaesthetized with MS-222 at 3, 9 and 28 days post exposure and sampled aseptically. Each spleen was washed three times with sterile phosphate-buffered saline containing a cocktail of mammalian protease inhibitors. Spleen samples were snap-frozen in liquid nitrogen and stored at –80 °C.

2018-08-14 | PXD008478 | Pride

Shotgun proteomic profiling of head kidney of rainbow trout Oncorhynchus mykiss

Project description:The objective of this study was to identify and quantify proteomic profiles of head kidney of rainbow trout Oncorhynchus mykiss. Specific pathogen free rainbow trout (mean length 15 ± 1 cm) were maintained in recirculating de-chlorinated water at 19±1 °C. Prior to the experiment, fish were distributed between 9 aquaria, 18 fish per aquarium. The test groups were infected by immersion of Yersinia ruckeri strains: CSF007-82 (biotype 1) and 7959-11 (biotype 2). The control group was immersed similar with sterile broth medium. There were 3 aquaria per each group (CSF007-82-infected, 7959-11-infected and control). Nine fish from infected and control fish groups were anaesthetized with MS-222 at 3, 9 and 28 days post exposure and sampled aseptically. Each head kidney was washed three times with sterile phosphate-buffered saline containing a cocktail of mammalian protease inhibitors. Head kidney samples were snap-frozen in liquid nitrogen and stored at –80 °C.

2018-08-14 | PXD008473 | Pride

Limiting the buffer function of HSP90 enhances tumor immunogenicity

Project description:MC38 cells were treated with HSP90 inhibitor and antigen repertoires were analyzed via mass spectrometry.

2019-06-26 | PXD009542 | Pride