A requirement for bid for induction of apoptosis by photodynamic therapy with a lysosome- but not a mitochondrion-targeted photosensitizer.
Photodynamic therapy (PDT) with lysosome-targeted photosensitizers induces the intrinsic pathway of apoptosis via the cleavage and activation of the BH3-only protein Bid by proteolytic enzymes released from photodisrupted lysosomes. To investigate the role of Bid in apoptosis induction and the role of damaged lysosomes on cell killing by lysosome-targeted PDT, we compared the responses of wild type and Bid-knock-out murine embryonic fibroblasts toward a mitochondrion/endoplasmic reticulum-binding photosensitizer, Pc 4, and a lysosome-targeted sensitizer, Pc 181. Whereas apoptosis and overall cell killing were induced equally well by Pc 4-PDT in both cell lines, Bid(-/-) cells were relatively resistant to induction of apoptosis and to overall killing following PDT with Pc 181, particularly at low PDT doses. Thus, Bid is critical for the induction of apoptosis caused by PDT with the lysosome-specific sensitizers, but dispensable for PDT targeted to other membranes.
Chiu
Song-Mao
SM
Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
Xue
Liang-Yan
LY
Lam
Minh
M
Rodriguez
Myriam E
ME
Zhang
Ping
P
Kenney
Malcolm E
ME
Nieminen
Anna-Liisa
AL
Oleinick
Nancy L
NL
D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D055786:Gene Knockout Techniques; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D009113:Muramidase / Q000187:drug effects / Q000528:radiation effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000528:radiation effects
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D017319:Photosensitizing Agents; D009113:Muramidase