{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ziogas A"],"funding":["NIDCR NIH HHS","Deutsche Forschungsgemeinschaft","National Institutes of Health"],"pagination":["e21425"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7909462"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["35(3)"],"pubmed_abstract":["Histamine-induced vascular leakage is a core process of allergic pathologies, including anaphylaxis. Here, we show that glycolysis is integral to histamine-induced endothelial barrier disruption and hyperpermeability. Histamine rapidly enhanced glycolysis in endothelial cells via a pathway that involved histamine receptor 1 and phospholipase C beta signaling. Consistently, partial inhibition of glycolysis with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) prevented histamine-induced hyperpermeability in human microvascular endothelial cells, by abolishing the histamine-induced actomyosin contraction, focal adherens junction formation, and endothelial barrier disruption. Pharmacologic blockade of glycolysis with 3PO in mice reduced histamine-induced vascular hyperpermeability, prevented vascular leakage in passive cutaneous anaphylaxis and protected from systemic anaphylaxis. In conclusion, we elucidated the role of glycolysis in histamine-induced disruption of endothelial barrier integrity. Our data thereby point to endothelial glycolysis as a novel therapeutic target for human pathologies related to excessive vascular leakage, such as systemic anaphylaxis."],"journal":["FASEB journal : official publication of the Federation of American Societies for Experimental Biology"],"pubmed_title":["Glycolysis is integral to histamine-induced endothelial hyperpermeability."],"pmcid":["PMC7909462"],"funding_grant_id":["R37 DE026152","DE026152","TR‐SFB 127"],"pubmed_authors":["Witt A","Grossklaus S","Ziogas A","Lim JH","Sajib MS","Hagag E","Sprott D","Mikelis CM","Mirtschink P","Grinenko T","Chavakis T","Gerlach M","Hajishengallis G","Alves TC","Das A","Androulaki N","Noll T"],"additional_accession":[]},"is_claimable":false,"name":"Glycolysis is integral to histamine-induced endothelial hyperpermeability.","description":"Histamine-induced vascular leakage is a core process of allergic pathologies, including anaphylaxis. Here, we show that glycolysis is integral to histamine-induced endothelial barrier disruption and hyperpermeability. Histamine rapidly enhanced glycolysis in endothelial cells via a pathway that involved histamine receptor 1 and phospholipase C beta signaling. Consistently, partial inhibition of glycolysis with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) prevented histamine-induced hyperpermeability in human microvascular endothelial cells, by abolishing the histamine-induced actomyosin contraction, focal adherens junction formation, and endothelial barrier disruption. Pharmacologic blockade of glycolysis with 3PO in mice reduced histamine-induced vascular hyperpermeability, prevented vascular leakage in passive cutaneous anaphylaxis and protected from systemic anaphylaxis. In conclusion, we elucidated the role of glycolysis in histamine-induced disruption of endothelial barrier integrity. Our data thereby point to endothelial glycolysis as a novel therapeutic target for human pathologies related to excessive vascular leakage, such as systemic anaphylaxis.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-06-01T02:09:23.387Z","creation":"2025-04-04T19:54:06.168Z"},"accession":"S-EPMC7909462","cross_references":{"pubmed":["33566443"],"doi":["10.1096/fj.202001634R"]}}