title: The 18 kDa mitochondrial translocator protein (TSPO) prevents accumulation of protoporphyrin IX. Involvement of reactive oxygen species (ROS).
abstract: By exposing cells of the U118MG glioblastoma cell line to protoporphyrin IX (PPIX) in culture, we found that the 18 kDa mitochondrial translocator protein (TSPO) prevents intracellular accumulation of PPIX. In particular, TSPO knockdown by stable transfection of TSPO silencing siRNA vectors into U118MG cells leads to mitochondrial PPIX accumulation. In combination with light exposure, the PPIX accumulation led to cell death of the TSPO knockdown cells. In the sham control cells (stable transfection of scrambled siRNA vectors), TSPO expression remained high and no PPIX accumulation was observed. The prevention of PPIX accumulation by TSPO was not due to conversion of PPIX to heme in the sham control cells. Similar to TSPO knockdown, the reactive oxygen species (ROS) scavenger glutathione (GSH) also enhanced PPIX accumulation. This suggests that that ROS generation as modulated by TSPO activation may present a mechanism to prevent accumulation of PPIX.
authors.affiliation: Department of Molecular Pharmacology, Technion-Israel Institute of Technology, Ephron Street, P.O. Box 9649, Bat-Galim, Haifa 31096, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Zeno
authors.forename: L
authors.initials: L
authors.lastname: Veenman
authors.forename: Y
authors.initials: Y
authors.lastname: Katz
authors.forename: J
authors.initials: J
authors.lastname: Bode
authors.forename: M
authors.initials: M
authors.lastname: Gavish
authors.forename: M
authors.initials: M
authors.lastname: Zaaroor
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D005978:Glutathione / Q000494:pharmacology; D006418:Heme / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D011524:Protoporphyrins / Q000378:metabolism / Q000494:pharmacology*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016166:Free Radical Scavengers; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D018079:Receptors, GABA; C499229:TSPO protein, human; D006418:Heme; C028025:protoporphyrin IX; D005978:Glutathione