PXD002787

PXD002787 is an original dataset announced via ProteomeXchange.

Title	Developmental alcohol exposure leads to a persistent change on astrocyte secretome
Description	Glial cells are central players in the pathogenesis of neurodevelopmental disorders like Fetal Alcohol Spectrum Disorder (FASD). Ethanol can modulate glial differentiation and astrocyte function imposing dramatic changes to the developing brain. Since ethanol can affect a vast number of intracellular targets and signaling pathways and many effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to a long-lasting change in astrocyte secretome in vitro. Animals were treated every other day with ethanol (5g/kg) or saline between post-natal day (P)10-30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids (SILAC). 24h-conditioned media of cells obtained from ethanol- or saline-treated animals (ET-CM or SAL-CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET-CM to SAL-CM. Among 59 proteins found reduced in ET-CM we found components of the extracellular matrix like Laminin subunits α2, α4, β1, β2 and γ1 and the proteoglycans Biglycan, Heparin Sulfate Proteoglycan 2 and Lumican. Proteins with trophic function like Insulin-Like Growth Factor Binding Protein 4, Pigment Epithelium-Derived Factor and Clusterin as well as proteins involved on modulation of proteolysis like TIMP-1 and PAI-1 were also found reduced. On the other hand, pro-synaptogeneic proteins like Thrombospondin-1, Hevin as well as the modulator of extracelular matrix expression, Angiotensinogen, were found increased in ET-CM. The analysis of interactome maps through Ingenuity Pathway Analysis demonstrated that the Amyloid beta A4 protein precursor (APP), which was found reduced in ET-CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET-CM, rendering it a suitable target for a more accurate analysis about the effects of ethanol on its biology. Taken together our results strongly suggest that early exposure to teratogens such alcohol may lead to an enduring change in astrocyte secretome, affecting mainly the expression of trophic and matricellular proteins, which in turn may lead to permanent alterations in brain function.
HostingRepository	PRIDE
AnnounceDate	2016-02-15
AnnouncementXML	Submission_2016-02-15_03:39:28.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pablo Trindade
SpeciesList	scientific name: Mustela putorius furo (European domestic ferret) (Mustela furo); NCBI TaxID: 9669;
ModificationList	iodoacetamide derivatized residue; 6x(13)C labeled L-lysine
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-25 01:22:08	ID requested
⏵ 1	2016-02-15 03:39:29	announced

Trindade P, Hampton B, Manh, ã, es AC, Medina AE, Developmental alcohol exposure leads to a persistent change on astrocyte secretome. J Neurochem, 137(5):730-43(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Astrocytes, Secretome, Ethanol, FASD

Alexandre E. Medina de Jesus, D.Sci.
contact affiliation	Department of Pediatrics University of Maryland, School of Medicine
contact email	amedinadejesus@peds.umaryland.edu
lab head
Pablo Trindade
contact affiliation	University of Maryland, Baltimore
contact email	pablotrindade@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002787
     1. Label: PRIDE project
     2. Name: Developmental alcohol exposure leads to a persistent change on astrocyte secretome