English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Delivery of cargo to cells through the use of cell-penetrating peptide (CPP) sequences is an area of rich investigation for targeted therapeutics. Specific to the endothelium, the layer of cells that cover every blood vessel in the body, the loss or alteration of a key enzyme, endothelial nitric oxide synthase (eNOS), is known to contribute to endothelial health during severe, infectious challenge. While the beneficial effects of eNOS are often thought to be mediated through the generation of nitric oxide, some protection is theorized to be through eNOS binding to regulatory pathways via a pentabasic RRKRK motif. We hypothesized that delivery of the eNOS-RRKRK peptide sequence using common CPPs would allow protection against gram-negative lipopolysaccharide (LPS). Combination of the eNOS-RRKRK sequence to the CPP antennapedia (AP) reduced the impact of LPS-induced permeability in cultured human microvascular endothelial cells (HMVECs) as measured by transendothelial electrical resistance (TEER). There was also a modest reduction in cytokine production, however it was observed that AP alone significantly impaired LPS-induced endothelial permeability and cytokine production. In comparison, the CPP trans-activator of transcription (TAT) did not significantly alter endothelial inflammation by itself. When TAT was coupled to the eNOS-RRKRK sequence, protection against LPS-induced permeability was still demonstrated, however cytokine production was not reduced. These data demonstrate that the RRKRK sequence of eNOS can offer some NO-independent protection against LPS-mediated endothelial inflammation, however the degree of protection is highly dependent on the type of CPP utilized for cargo delivery.

Cell penetrating peptides coupled to an endothelial nitric oxide synthase sequence alter endothelial permeability