Biomembrane damage by a lipophilic photosensitizer

MARIANA VIGNONI; M. NOEL URRUTIA; HELENA C, JUNQUEIRA; ALEXANDER GREER; ANA REIS; MAURICIO S. BAPTISTA; ROSANGELA ITRI; ANDRÉS H. THOMAS

La Plata

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Pterinsare natural products that can photosensitize the oxidation of DNA, proteins andphospholipids.1,2,3 Recently, a new series of lipophilic pterinswere synthesized and their photophysical properties investigated.4These decyl-pterins led to efficient intercalation in large unilamellarvesicles and produce, under UVA irradiation, singlet molecular oxygen, a highlyoxidative species that react with polyunsaturated fatty acids (PUFAs) to formhydroperoxides. Here,we demonstrate that the association of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) to lipid membranes is keyto its ability to trigger phospholipid oxidation in unilamellar vesicles of phosphatidylcholine rich in PUFAs used as modelbiomembranes. Our results show that O-decyl-Ptris at least one order of magnitude more efficient photosensitizer of lipidsthan pterin (Ptr), the unsubstituted derivative of the pterin family, which ismore hydrophilic and freely passes across lipid membranes. Lipid peroxidationphotosensitized by O-decyl-Ptr wasdetected by the formation of conjugated dienes and oxidized lipids, such as hydroxyand hydroperoxides derivatives. These primary products undergo a rapidconversion into short-chain secondary products by cleavage of the fatty acidchains some of which are due to subsequent photosensitized reactions. As aconsequence, a fast increase in membrane permeability is observed. Therefore,lipid oxidation induced by O-decyl-Ptrcould promote cell photodamage due to the biomembrane integrity loss which, inturn, may trigger cell death.