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...
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| Veröffentlicht in: | Photochemistry and photobiology 2010-09, Vol.86 (5), p.1161-1173 |
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| container_title | Photochemistry and photobiology |
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| creator | Chiu, Song-mao Xue, Liang-yan Lam, Minh Rodriguez, Myriam E. Zhang, Ping Kenney, Malcolm E. Nieminen, Anna-Liisa Oleinick, Nancy L. |
| description | 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. |
| doi_str_mv | 10.1111/j.1751-1097.2010.00766.x |
| format | Article |
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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.</description><identifier>ISSN: 0031-8655</identifier><identifier>EISSN: 1751-1097</identifier><identifier>DOI: 10.1111/j.1751-1097.2010.00766.x</identifier><identifier>PMID: 20553412</identifier><identifier>CODEN: PHCBAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Autophagy ; BH3 Interacting Domain Death Agonist Protein - genetics ; BH3 Interacting Domain Death Agonist Protein - physiology ; Blotting, Western ; Cancer ; Cell Survival - drug effects ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; Gene Knockout Techniques ; Microscopy ; Mitochondria ; Mitochondria - drug effects ; Molecular Structure ; Muramidase - drug effects ; Muramidase - radiation effects ; Photochemotherapy ; Photodynamic therapy ; Photosensitizing Agents - radiation effects ; Proteins</subject><ispartof>Photochemistry and photobiology, 2010-09, Vol.86 (5), p.1161-1173</ispartof><rights>2010 The Authors. 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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.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy</subject><subject>BH3 Interacting Domain Death Agonist Protein - genetics</subject><subject>BH3 Interacting Domain Death Agonist Protein - physiology</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Cell Survival - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Delivery Systems</subject><subject>Gene Knockout Techniques</subject><subject>Microscopy</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Molecular Structure</subject><subject>Muramidase - drug effects</subject><subject>Muramidase - radiation effects</subject><subject>Photochemotherapy</subject><subject>Photodynamic therapy</subject><subject>Photosensitizing Agents - radiation effects</subject><subject>Proteins</subject><issn>0031-8655</issn><issn>1751-1097</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUV1v0zAUtRCIlcFfQBbvKf6I7URCSGWDblI3KlQ03iwncRaXNs5shzX8BH41zjIqeMMv1zr3nHPv1QEAYjTH8b3dzrFgOMEoF3OCIoqQ4Hx-eAJmx8ZTMEOI4iTjjJ2AF95vEcJpLvBzcEIQYzTFZAZ-LeAXfdcbp_e6DbC2Dn4w1UO9bKu-DMa20NZw0dkuWG88LAa4bmyw1dCqvSnhptFOdQO8N6GBCq4Gb73d6wQWfYDXNkTsygRbNratXHRLgnK3OuhqsvG69SaYn9q9BM9qtfP61WM9BV8_fdycXSSrz8vLs8UqKRkVPKE01XmpmWZlldcZVjkTjORYiTpVdYVHRHGMUqpIEY9UBU5xTRTLhWKi5vQUvJ98u77Y66qMdzu1k50ze-UGaZWR_3Za08hb-0OSXKQZyqLBm0cDZ-967YPc2t61cWcpOCGUID6SsolUOuu90_VxAEZyDFFu5ZiVHLOSY4jyIUR5iNLXfy94FP5JLRLeTYR7s9PDfxvL9cU6fqI8meTGB304ypX7Lrmggsmb66W8-nazOV_xc7mkvwEHtb0S</recordid><startdate>201009</startdate><enddate>201009</enddate><creator>Chiu, Song-mao</creator><creator>Xue, Liang-yan</creator><creator>Lam, Minh</creator><creator>Rodriguez, Myriam E.</creator><creator>Zhang, Ping</creator><creator>Kenney, Malcolm E.</creator><creator>Nieminen, Anna-Liisa</creator><creator>Oleinick, Nancy L.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>4T-</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>201009</creationdate><title>A Requirement for Bid for Induction of Apoptosis by Photodynamic Therapy with a Lysosome- but Not a Mitochondrion-targeted Photosensitizer</title><author>Chiu, Song-mao ; 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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Apoptosis Apoptosis - drug effects Autophagy BH3 Interacting Domain Death Agonist Protein - genetics BH3 Interacting Domain Death Agonist Protein - physiology Blotting, Western Cancer Cell Survival - drug effects Dose-Response Relationship, Drug Drug Delivery Systems Gene Knockout Techniques Microscopy Mitochondria Mitochondria - drug effects Molecular Structure Muramidase - drug effects Muramidase - radiation effects Photochemotherapy Photodynamic therapy Photosensitizing Agents - radiation effects Proteins |
| title | A Requirement for Bid for Induction of Apoptosis by Photodynamic Therapy with a Lysosome- but Not a Mitochondrion-targeted Photosensitizer |
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