dc.contributor.author |
Coutinho, Frazer P |
|
dc.contributor.author |
Green, Colin R |
|
dc.contributor.author |
Acosta, Monica L |
|
dc.contributor.author |
Rupenthal, Ilva D |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2023-10-06T00:30:49Z |
|
dc.date.available |
2023-10-06T00:30:49Z |
|
dc.date.issued |
2020-06 |
|
dc.identifier.citation |
(2020). Drug Delivery and Translational Research, 10(3), 751-765. |
|
dc.identifier.issn |
2190-393X |
|
dc.identifier.uri |
https://hdl.handle.net/2292/66172 |
|
dc.description.abstract |
Hypoxic injury results in cell death, tissue damage and activation of inflammatory pathways. This is mediated by pathological Connexin43 (Cx43) hemichannel (HC) opening resulting in osmotic and ionic imbalances as well as cytokine production perpetuating the inflammatory environment. Gap19 is an intracellularly acting Cx43 mimetic peptide that blocks HC opening and thus promotes cell survival. However, native Gap19, which must enter the cell in order to function, exhibits low cell permeability. In this study, Gap19 was conjugated to the cell-penetrating peptide, Xentry, to investigate if cellular uptake could be improved while maintaining peptide function. Cellular uptake of Xentry-Gap19 (XG19) was much greater than that of native Gap19 even under normal cell culture conditions. Peptide function was maintained post uptake as shown by reduced ethidium homodimer influx and ATP release due to Cx43 HC block. While XG19 blocked pathologic HC opening though, normal gap junction communication required for cell repair and survival mechanisms was not affected as shown in a dye scrape-load assay. Under hypoxic conditions, increased expression of Syndecan-4, a plasma membrane proteoglycan targeted by Xentry, enabled even greater XG19 uptake leading to higher inhibition of ATP release and greater cell survival. This suggests that XG19, which is targeted specifically to hypoxic cells, can efficiently and safely block Cx43 HC and could therefore be a novel treatment for hypoxic and inflammatory diseases. Graphical abstract. |
|
dc.format.medium |
Print |
|
dc.language |
eng |
|
dc.publisher |
Springer Nature |
|
dc.relation.ispartofseries |
Drug delivery and translational research |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
Cell Line |
|
dc.subject |
Gap Junctions |
|
dc.subject |
Humans |
|
dc.subject |
Peptide Fragments |
|
dc.subject |
Connexin 43 |
|
dc.subject |
Cell Hypoxia |
|
dc.subject |
Gene Expression Regulation |
|
dc.subject |
Molecular Mimicry |
|
dc.subject |
Syndecan-4 |
|
dc.subject |
Cell-Penetrating Peptides |
|
dc.subject |
Cell-penetrating peptide |
|
dc.subject |
Connexin43 |
|
dc.subject |
Gap19 |
|
dc.subject |
Hemichannel |
|
dc.subject |
Hypoxia |
|
dc.subject |
Mimetic peptide |
|
dc.subject |
Xentry |
|
dc.subject |
3208 Medical Physiology |
|
dc.subject |
32 Biomedical and Clinical Sciences |
|
dc.subject |
Biotechnology |
|
dc.subject |
1 Underpinning research |
|
dc.subject |
2 Aetiology |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
1.1 Normal biological development and functioning |
|
dc.subject |
Science & Technology |
|
dc.subject |
Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Instruments & Instrumentation |
|
dc.subject |
Medicine, Research & Experimental |
|
dc.subject |
Pharmacology & Pharmacy |
|
dc.subject |
Research & Experimental Medicine |
|
dc.subject |
RETINAL-PIGMENT EPITHELIUM |
|
dc.subject |
MIMETIC PEPTIDES |
|
dc.subject |
GAP-JUNCTIONS |
|
dc.subject |
CELL-DEATH |
|
dc.subject |
MACULAR DEGENERATION |
|
dc.subject |
GROWTH-FACTORS |
|
dc.subject |
BLOOD-FLOW |
|
dc.subject |
SYNDECAN 4 |
|
dc.subject |
IN-VITRO |
|
dc.subject |
EXPRESSION |
|
dc.subject |
0601 Biochemistry and Cell Biology |
|
dc.subject |
Biomedical |
|
dc.subject |
Basic Science |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.subject |
3214 Pharmacology and pharmaceutical sciences |
|
dc.title |
Xentry-Gap19 inhibits Connexin43 hemichannel opening especially during hypoxic injury. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1007/s13346-020-00763-y |
|
pubs.issue |
3 |
|
pubs.begin-page |
751 |
|
pubs.volume |
10 |
|
dc.date.updated |
2023-09-08T03:57:53Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
32318976 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/32318976 |
|
pubs.end-page |
765 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RetrictedAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
801772 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
School of Medicine |
|
pubs.org-id |
Ophthalmology Department |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
pubs.org-id |
Optometry and Vision Science |
|
dc.identifier.eissn |
2190-3948 |
|
dc.identifier.pii |
10.1007/s13346-020-00763-y |
|
pubs.record-created-at-source-date |
2023-09-08 |
|
pubs.online-publication-date |
2020-04-21 |
|