Statin-boosted cellular uptake and endosomal escape of penetratin due to
reduced membrane dipole potential
- Gyula Batta,
- Levente Karpati,
- Gabriela Fulaneto,
- Szabolcs Tarapcsak,
- Tamas Kovacs,
- Florina Zakany,
- Istvan Mandity,
- Peter Nagy
Abstract
Since cell penetrating peptides are promising tools for delivery of
cargo into cells, factors limiting or facilitating their cellular uptake
are intensely studied. Using labeling with pH-insensitive and
pH-sensitive dyes we report that escape of penetratin from acidic
endo-lysosomal compartments is retarded compared to its total cellular
uptake. The membrane dipole potential, known to alter transmembrane
transport of charged molecules, is shown to be negatively correlated
with the concentration of penetratin in the cytoplasmic compartment.
Treatment of cells with therapeutically relevant concentrations of
atorvastatin, an inhibitor of HMG-CoA reductase and cholesterol
synthesis, significantly increased endosomal escape of penetratin in two
different cell types. This effect of atorvastatin correlated with its
ability to decrease the membrane dipole potential. These results
highlight the importance of the dipole potential in regulating cellular
uptake of cell penetrating peptides and suggest a clinically relevant
way of boosting this process.22 Sep 2020Submitted to British Journal of Pharmacology 23 Sep 2020Submission Checks Completed
23 Sep 2020Assigned to Editor
29 Sep 2020Reviewer(s) Assigned
01 Nov 2020Review(s) Completed, Editorial Evaluation Pending
14 Nov 2020Editorial Decision: Revise Minor
21 Mar 20211st Revision Received
22 Mar 2021Submission Checks Completed
22 Mar 2021Assigned to Editor
27 Mar 2021Reviewer(s) Assigned
05 Apr 2021Review(s) Completed, Editorial Evaluation Pending
18 Apr 2021Editorial Decision: Revise Minor
19 Apr 20212nd Revision Received
20 Apr 2021Submission Checks Completed
20 Apr 2021Assigned to Editor
24 Apr 2021Editorial Decision: Accept