Effect of Adriamycin on the boundary lipid structure of cytochrome c oxidase: pico-second time-resolved fluorescence depolarization studies.
The fluorescence dynamics of the dye 3,3'-diethyloxadicarbocyanine iodide (DODCI) was used to probe the microenvironment of cytochrome c oxidase (CcO) and cardiolipin. The dye was partitioned between an aqueous and a hydrophobic phase. The 'bound' and 'free' populations of DODCI could be separated by analysis of the time-resolved fluorescence decay of the dye. The anisotropy decay of the DODCI bound to CcO showed a unique 'dip and rise' shape that was analyzed by a combination of rotational correlation times with time-dependent weight factors for each lifetime component. Rotational dynamics studies revealed the existence of a restricted motion of the dye bound at the enzyme surface. Adriamycin, an anticancer, albeit cardiotoxic drug, was previously proposed to affect the surface structure of CcO, most likely by causing a disorder to the surface lipid arrangement. A drastic change in the rotational correlation time of the dye bound to the enzyme surface was observed, which suggested a depletion of cardiolipin layer due to complexation with the drug. The effect of Adriamycin on cardiolipin was drastic, leading to its phase separation. The present study suggests that the effect of Adriamycin on CcO is primarily a segregation of the cardiolipins.
Das
T K
TK
Albert Einstein College of Medicine, Bronx, NY 10461, USA. tdas@aecom.yu.edu
Mazumdar
S
S
D000465:Algorithms; D000818:Animals; D016880:Anisotropy; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D002308:Cardiolipins / Q000737:chemistry; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003902:Detergents; D004317:Doxorubicin / Q000737:chemistry*; D003576:Electron Transport Complex IV / Q000737:chemistry*; D016231:Fluorescence Polarization Immunoassay; D008055:Lipids / Q000737:chemistry*; D010713:Phosphatidylcholines; D010743:Phospholipids / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D002308:Cardiolipins; D003902:Detergents; D008055:Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; C024990:asolectin; D004317:Doxorubicin; D003576:Electron Transport Complex IV