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Proceedings Paper

Role of mitochondrial photodamage in PDT-induced apoptosis
Author(s): Yu Luo; Zhuoyan Zhang; David Kessel
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Paper Abstract

PDT with sensitizers that target mitochondria for photodamage induces a rapid apoptotic response in murine leukemia cells. Immediately after irradiation, we observed loss of the mitochondrial membrane potential ((Delta) (Psi) m), and transfer of cytochrome c from mitochondria to the cytosol. Within 3 min, there was a marked increase in caspase-3 activity, but not of caspases 1,4,5,6 or 8. While phosphorylation of a tyrosine residue on an 85 kDa protein was a prominent consequence of PDT, this was inhibited by the protein kinase C inhibitor staurosporin, a drug which enhanced the apoptotic response to PDT. Tyrosine phosphorylation may therefore not be a requisite for PDT-induced apoptosis. These results are consistent with a mechanism whereby mitochondrial photodamage, leading to the release of cytochrome c (and perhaps other factors), can directly trigger caspase activation and apoptosis. We have previously reported that the apoptotic response to PDT was delayed when both mitochondria and the plasma membrane were targeted for photodamage. We found that the membrane photodamage resulted in inhibition of neutral sphingomyelinase activity. This enzyme is one source of ceramide biosynthesis, suggesting that ceramide formation via sphingomyelinase activity enhances the apoptotic response to PDT.

Paper Details

Date Published: 19 May 1998
PDF: 6 pages
Proc. SPIE 3247, Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII, (19 May 1998); doi: 10.1117/12.308138
Show Author Affiliations
Yu Luo, Wayne State Univ. School of Medicine (United States)
Zhuoyan Zhang, Wayne State Univ. School of Medicine (United States)
David Kessel, Wayne State Univ. School of Medicine (United States)


Published in SPIE Proceedings Vol. 3247:
Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII
Thomas J. Dougherty, Editor(s)

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