Title of article :
“Mitochondrial” photochemical drugs do not release toxic amounts of 1O2 within the mitochondrial matrix space
Author/Authors :
Petrat، نويسنده , , Frank and Pindiur، نويسنده , , Stanislaw and Kirsch، نويسنده , , Michael and de Groot، نويسنده , , Herbert، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2003
Abstract :
Previously, we demonstrated that mitochondrial NAD(P)H is the primary target of singlet oxygen (1O2) generated by photoactivation of mitochondria-selective rhodamine derivatives. Hence, local NAD(P)H oxidation/fluorescence decrease may be used to reveal the site of intracellular 1O2 generation. Therefore, in addition to the previously used tetramethylrhodamine methylester (TMRM), 2′,4′,5′,7′-tetrabromorhodamine 123 bromide (TBRB) and rhodamine 123 (Rho 123), we tested here whether mitochondrial NAD(P)H of cultured hepatocytes is directly oxidized upon irradiation of different “mitochondrial” photosensitizers (Photofrin; protoporphyrin IX; Al(III) phthalocyanine chloride tetrasulfonic acid; meso-tetra(4-sulfonatophenyl)porphine dihydrochloride; Visudyne). In contrast to TMRM and Rho 123, which directly oxidized NAD(P)H upon irradiation, irradiation of intracellular TBRB and the photochemical drugs only indirectly affected mitochondrial NAD(P)H due to loss of mitochondrial integrity. In line with this result only TMRM and Rho 123 exclusively localized within the mitochondrial matrix. Due to these results it is doubtful whether real mitochondrial photosensitizers actually exist among the photochemical drugs applicable/used for photodynamic therapy.
Keywords :
Pyridine nucleotides , singlet oxygen , photodynamic therapy , Rhodamine 123 , Metabolic compartmentation , Mitochondria , NAD(P)H , Photosensitizers , Tetramethylrhodamine methylester
Journal title :
Archives of Biochemistry and Biophysics
Journal title :
Archives of Biochemistry and Biophysics