Photo-Oxidation of Unilamellar Vesicles by a Lipophilic Pterin: Deciphering Biomembrane Photodamage

Author(s)

Vignoni, Mariana ^[1] ; Noel Urrutia, Maria ^[1] ; Junqueira, Helena C. ^[2] ; Greer, Alexander ^{[3, 4]} ; Reis, Ana ^[5] ; Baptista, Mauricio S. ^[2] ; Itri, Rosangela ^[6] ; Thomas, Andres H. ^[1]

Affiliation

^[1] Univ Nacl La Plata, CONICET, Inst Invest Fisicoquim Teor & Aplicadas, Dept Quim, Fac Cs Exactas, CCT La Plata, CC 16, Suc 4, RA-1900 La Plata, Buenos Aires - Argentina

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil

^[3] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 - USA

^[4] CUNY, Grad Ctr, PhD Program Chem, 365 Fifth Ave, New York, NY 10016 - USA

^[5] Univ Porto, Fac Sci, Dept Chem & Biochem, ICETA, REQUIMTE, LAQV, P-4169007 Porto - Portugal

^[6] Univ Sao Paulo, Inst Phys, BR-05508090 Sao Paulo - Brazil

• Document type: Journal article
• Source: Langmuir; v. 34, n. 50, p. 15578-15586, DEC 18 2018.
• Web of Science Citations: 4

Abstract

Pterins are natural products that can photosensitize the oxidation of DNA, proteins, and phospholipids. Recently, a new series of decyl-chain (i.e., lipophilic) pterins were synthesized and their photophysical properties were investigated. These decyl-pterins led to efficient intercalation in large unilamellar vesicles and produced, under UVA irradiation, singlet molecular oxygen, a highly oxidative species that react with polyunsaturated fatty acids (PUFAs) to form hydroperoxides. Here, we demonstrate that the association of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) to lipid membranes is key to its ability to trigger phospholipid oxidation in unilamellar vesicles of phosphatidylcholine rich in PUFAs used as model biomembranes. Our results show that O-decyl-Ptr is at least 1 order of magnitude more efficient photosensitizer of lipids than pterin (Ptr), the unsubstituted derivative of the pterin family, which is more hydrophilic and freely passes across lipid membranes. Lipid peroxidation photosensitized by O-decyl-Ptr was detected by the formation of conjugated dienes and oxidized lipids, such as hydroxy and hydroperoxide derivatives. These primary products undergo a rapid conversion into short-chain secondary products by cleavage of the fatty-acid chains, some of which are due to subsequent photosensitized reactions. As a consequence, a fast increase in membrane permeability is observed. Therefore, lipid oxidation induced by O-decyl-Ptr could promote cell photodamage due to the biomembrane integrity loss, which in turn may trigger cell death. (AU)

• FAPESP's process: 16/04296-0 - Photosensitization and photodamage of cells and biomimetic models by pterin derivatives
• Grantee: Mauricio da Silva Baptista
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/50680-5 - Photosensitization in life sciences
• Grantee: Mauricio da Silva Baptista
• Support Opportunities: Research Projects - Thematic Grants