PXD001834

PXD001834 is an original dataset announced via ProteomeXchange.

Title	Adaptative changes in protein expression and lysine acetylation induced by decreased glutathione levels in astrocytes
Description	Astrocytes and neurons form a highly specialized functional unit and the loss or gain of astrocytic functions can influence the initiation and progression of different neurodegenerative diseases. Neurons depend on the antioxidant protection provided by neighboring astrocytes. Glutathione (-l-glutamyl-l-cysteinyl-glycine) is a major component of the antioxidant system that defends cells against the toxic effects of reactive oxygen/nitrogen species. A decline in glutathione levels has been observed in aging and neurodegenerative diseases and it aggravates the pathology in an amyotrophic lateral sclerosis-mouse model. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic approach, we analyzed the changes in global protein expression and regulation of lysine acetylation, in primary astrocyte cultures obtained from wild type mice or those deficient in the glutamate-cysteine ligase modifier subunit (GCLM). GCLM knockout astrocytes display an approximately 80% reduction in total glutathione levels. We identified potential molecular targets that are affected by the chronic decrease in glutathione levels and observed an adaptative response mediated by Nrf2 activation. In addition, sequence analysis of peptides more extensively acetylated in the absence of GCLM revealed an enrichment of cysteine residues immediately surrounding the site of acetylation; which suggests a potential specific regulation by decreased glutathione content. Pathway analysis revealed that some pathways exhibited both differential protein expression and lysine acetylation, revealing a coordinated response involving transcriptional and post-translational regulation.
HostingRepository	PRIDE
AnnounceDate	2017-10-24
AnnouncementXML	Submission_2017-10-24_00:26:28.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-02-22 23:51:11	ID requested
1	2015-10-24 10:42:40	announced
2	2017-06-21 00:31:00	announced	Updated project metadata.
⏵ 3	2017-10-24 00:26:30	announced	Updated project metadata.

Pehar M, Ball LE, Sharma DR, Harlan BA, Comte-Walters S, Neely BA, Vargas MR, Changes in Protein Expression and Lysine Acetylation Induced by Decreased Glutathione Levels in Astrocytes. Mol Cell Proteomics, 15(2):493-505(2016) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: SILAC, Acetyl, Astrocytes

Lauren Ball
contact affiliation	Department of Pharmacology Director of Proteomics Mass Spectrometry Facility
contact email	ballle@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001834
     1. Label: PRIDE project
     2. Name: Adaptative changes in protein expression and lysine acetylation induced by decreased glutathione levels in astrocytes