MassIVE MSV000097979

Partial Public

Per- and polyfluoroalkyl substances induce cardiotoxicity and alter protein profiles related to extracellular matrix, metabolism and mitochondrial function in human cardiomyocytes

Subscribe Comment Convert Spectra Reanalyze Spectra Add Reanalysis

Description

Per- and polyfluoroalkyl substances (PFASs), common environmental contaminants, can cause cardiotoxic effects particularly during fetal development. However, combined PFAS exposure, which more closely reflects real-world environmental conditions, remains poorly understood. In this study, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to three common PFAS compounds-perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorodecanoic acid (PFDA), individually or in combination. Compared with single PFAS compounds, combined PFAS exposure induced synergistic cytotoxicity, significantly reducing hiPSC-CM viability after 5 or 10 days. Combined PFAS exposure for 10 days reduced mitochondrial membrane potential and content in a dose-dependent manner and caused a shift in cysteine metabolism, potentially indicative of an adaptive response to oxidative challenges. Following 14 days of exposure, combined PFASs increased vimentin, a fibroblast marker, along with reduced NK2 Homeobox 5 (NKX2.5), alpha-actinin, and cardiac troponin T (cTnT), key markers of cardiomyocytes, as detected by immunocytochemistry. In addition, proteomic profiling identified that combined PFASs upregulated proteins related to extracellular matrix organization, cholesterol metabolism, and antioxidant defense, and downregulated proteins related to mitochondrial function. These results underscore the importance of evaluating PFAS mixtures to better understand cardiac risks associated with environmental exposure. [doi:10.25345/C5B56DH5Q] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Per- and polyfluoroalkyl substances ; cardiotoxicity ; hiPSC-derived cardiomyocytes ; mitochondrial dysfunction ; extracellular matrix ; metabolism ; proteomics ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Chunhui Xu, Department of Pediatrics, Emory University School of Medicine, USA
Submitting User: Zeyu
Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.