PXD021040

PXD021040 is an original dataset announced via ProteomeXchange.

Title	Disruption of endothelial glycocalyx after ischemic stroke onset: Activated scission activity of proHPSE by acrolein exposure
Description	Infiltration of peripheral immune cells after blood-brain barrier (BBB) dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans (GAGs), a component of the endothelial glycocalyx, in ischemic stroke were studied using a photochemically induced thrombosis (PIT) mouse model. As results, decreased levels of heparan sulfate (HS) and chondroitin sulfate (CS) and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine (NAC)+GAG oligosaccharides as compared to NAC administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by HBMEC/ciβ and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein exposure. We identified the ACR modified amino acid residues of proHPSE using nano LC-MS/MS, suggesting that ACR modification of Lys139 (6-kDa linker), and Lys107 and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part, is attributed to the activation of proHPSE. Since proHPSE, but not HPSE, localizes outside cells by binding with HS proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx.
HostingRepository	PRIDE
AnnounceDate	2020-11-16
AnnouncementXML	Submission_2020-11-16_14:12:25.xml
DigitalObjectIdentifier	http://dx.doi.org/10.6019/PXD021040
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Takehiro Suzuki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine; monohydroxylated residue; deaminated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-20 23:44:04	ID requested
⏵ 1	2020-11-16 14:12:26	announced

Ko K, Suzuki T, Ishikawa R, Hattori N, Ito R, Umehara K, Furihata T, Dohmae N, Linhardt RJ, Igarashi K, Toida T, Higashi K, Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure. J Biol Chem, 295(52):18614-18624(2020) [pubmed]

submitter keyword: acrolein heparanase

Naoshi Dohmae
contact affiliation	Biomolecular characterization unit, Center for Sustainable Resource Science, RIKEN
contact email	dohmae@riken.jp
lab head
Takehiro Suzuki
contact affiliation	RIKEN Center for Sustainable Resource Science
contact email	takehirosuzuki@riken.jp
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021040
     1. Label: PRIDE project
     2. Name: Disruption of endothelial glycocalyx after ischemic stroke onset: Activated scission activity of proHPSE by acrolein exposure