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A Requirement for Bid for Induction of Apoptosis by Photodynamic Therapy with a Lysosome‐ but Not a Mitochondrion‐targeted Photosensitizer
Author(s) -
Chiu Songmao,
Xue Liangyan,
Lam Minh,
Rodriguez Myriam E.,
Zhang Ping,
Kenney Malcolm E.,
Nieminen AnnaLiisa,
Oleinick Nancy L.
Publication year - 2010
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2010.00766.x
Subject(s) - lysosome , photodynamic therapy , apoptosis , microbiology and biotechnology , photosensitizer , endoplasmic reticulum , mitochondrion , chemistry , programmed cell death , biology , biochemistry , enzyme , organic chemistry
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.