Biomaterial Database

Initiation of apoptosis and autophagy by photodynamic therapy. 2006

David Kessel, and M Graça H Vicente, and John J Reiners

Departments of Pharmacology and Medicine, Wayne State University School of Medicine, Detroit Michigan 48201, USA. dhkessel@med.wayne.edu

OBJECTIVE This study was designed to examine modes of cell death after photodynamic therapy (PDT). METHODS Murine leukemia L1210 cells and human prostate Bax-deficient DU145 cells were examined after PDT-induced photodamage to the endoplasmic reticulum (ER). Phase contrast, fluorescence and electron microscopy were used to identify changes in cellular morphology, chromatin condensation, loss of mitochondrial membrane potential, and formation of phagolysosomes. Western blots were used to assess the processing of LC3-I to LC3-II, a marker for autophagy. Inhibitors of apoptosis and/or autophagy were used to delineate the contributions of the two pathways to the effects of PDT. RESULTS Both apoptosis and autophagy occurred in L1210 after ER photodamage with the latter predominating after 24 hours. In DU145 cells, PDT conditions causing comparable cytotoxicity only initiated autophagy. PI3-kinase inhibitors suppressed autophagy in both cell lines as indicated by inhibition of vacuolization and LC3 processing. CONCLUSIONS Both autophagy and apoptosis were observed in L1210 cells following ER photodamage. In the Bax-deficient DU145 cell line only autophagy was observed. Current information suggests that autophagy can function as either a survival or death pathway. We propose that in the context of PDT, this may also be true.

UI	MeSH Term	Description	Entries
D008854	Microscopy, Electron	Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.	Electron Microscopy
D008856	Microscopy, Fluorescence	Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.	Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D010447	Peptide Hydrolases	Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.	Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D010778	Photochemotherapy	Therapy using oral or topical photosensitizing agents with subsequent exposure to light.	Blue Light Photodynamic Therapy,Photodynamic Therapy,Red Light PDT,Red Light Photodynamic Therapy,Therapy, Photodynamic,Light PDT, Red,PDT, Red Light,Photochemotherapies,Photodynamic Therapies,Therapies, Photodynamic
D011166	Porphyrins	A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin.	Porphyrin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077191	Wortmannin	An androstadiene metabolite produced by the fungi PENICILLIUM funiculosum that inhibits PHOSPHATIDYLINOSITOL-3-KINASES and alloantigen-specific activation of T-LYMPHOCYTES in human tumor cell lines. It is widely used in CELL BIOLOGY research and has broad therapeutic potential.	MS 54,MS-54,MS54
D000730	Androstadienes	Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia