Protein kinase inhibitor effects on P-glycoprotein (P-gp) activity and expression in various cell lines
| dc.contributor.author | Pogorzelec, Michael P.J. | |
| dc.contributor.examiningcommittee | Hatch, Grant (Pharmacology and Therapeutics) Ho, Emmanuel (Pharmacy) Parkinson, Fiona (Pharmacology and Therapeutics) | en_US |
| dc.contributor.supervisor | Miller, Donald (Pharmacology and Therapeutics) | en_US |
| dc.date.accessioned | 2015-01-13T15:23:44Z | |
| dc.date.available | 2015-01-13T15:23:44Z | |
| dc.date.issued | 2015-01-13 | |
| dc.degree.discipline | Pharmacology and Therapeutics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Little is known about potential influences of kinase pathway modulation on expression and activity of P-glycoprotein (P-gp). A protein kinase inhibitor (PKI) library was screened, to determine its effects on activity and expression of P-gp, in various cell lines. Cell lines were incubated with PKI for 24 h. Subsequent P-gp substrate accumulation studies were performed. Changes in P-gp activity and/or expression ≥ 25% compared to control were considered hits. Kinase pathways identified as P-gp activity hits were examined for their ability to modulate permeability. PKI families GSK-3, Craf1 and VEGFR2 and Tie-2, significantly modulated P-gp activity in the MDCK cell line. PKI families GSK-3, Iκκ and Jnk2/3 significantly modulated P-gp activity in the Caco-2 cell line. Few P-gp activity hits significantly modulated P-gp expression. PKIs modulate P-gp activity more than P-gp expression in a cell line dependent manner, excluding GSK-3 PKI family, which appears to be cell line independent. | en_US |
| dc.description.note | February 2015 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/30206 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | P-glycoprotein | en_US |
| dc.subject | Protein kinase inhibitors | en_US |
| dc.subject | Blood Brain Barrier | en_US |
| dc.title | Protein kinase inhibitor effects on P-glycoprotein (P-gp) activity and expression in various cell lines | en_US |
| dc.type | master thesis | en_US |