ABSTRACT
Mitochondria-targeted antioxidants of the SkQR1 family, being accumulated in energized mitochondria, protect cells from oxidative stress by increasing the level of reduced glutathione and decreasing the cell-damaging effect induced by hydrogen peroxide. Using various human transformed cell lines and SkQR1 (a fluorescent member of the SkQ family), we show that SkQRI is ejected from chemotherapy-resistant cells by P-glycoprotein - one of the main transport proteins determining multidrug resistance typical for many neoplastic cells. It is also shown that SkQR1 ejection is neutralized by P-glycoprotein inhibitors (verapamil and pluronic L61). In experiments on K562 cells, it was found that the subline sensitive to chemotherapy is protected by SkQRI from apoptotic action of hydrogen peroxide. Protection of the resistant subline occurs only after inhibition of P-glycoprotein.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Mitochondria/metabolism , Neoplasms/metabolism , Plastoquinone/analogs & derivatives , Poloxamer/pharmacology , Rhodamines/pharmacology , Verapamil/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antioxidants/pharmacology , Calcium Channel Blockers/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Glutathione/biosynthesis , HeLa Cells , Humans , Hydrogen Peroxide/adverse effects , K562 Cells , Neoplasms/pathology , Oxidative Stress/drug effects , Plastoquinone/pharmacology , U937 CellsABSTRACT
Mitochondria-targeted antioxidants of the SkQRI family, being accumulated in energized mitochondria, protect cells from oxidative stress by increasing the level of reduced glutathione and decreasing the cell-damaging effect induced by hydrogen peroxide. Using various human transformed cell lines and SkQR1 (a fluorescent member of the SkQ family), we show that SkQR1 is ejected from chemotherapy-resistant cells by P-glycoprotein--one of the main transport proteins determining multidrug resistance typical for many neoplastic cells. It is also shown that SkQR1 ejection is neutralized by P-glycoprotein inhibitors (verapamil and pluronic L61). In experiments on K562 cells, it was found that the subline sensitive to chemotherapy is protected by SkQR1 from apoptotic action of hydrogen peroxide. Protection of the resistant subline occurs only after inhibition of P-glycoprotein.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antioxidants/pharmacology , Apoptosis/drug effects , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Plastoquinone/analogs & derivatives , Rhodamines/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Biological Transport/drug effects , Calcium Channel Blockers/pharmacology , HeLa Cells , Humans , K562 Cells , Plastoquinone/pharmacology , Poloxamer/pharmacology , U937 Cells , Verapamil/pharmacologyABSTRACT
The increase of Na+ concentration from the submillimolar level to 50 mM stimulates growth of the Escherichia coli cells in the presence of the protonophorous uncoupler CCCP. The half-maximal effects is observed at 1 mM Na+. The decrease of inorganic phosphate concentration from tens of millimoles to 0.5 mM inhibits cell growth under same conditions.
