Activation of the stress-activated JNK and p38 MAP kinases in human cells by Photofrin-mediated photodynamic therapy.
We have examined the possible role of the stress-activated JNK and p38 protein kinases in cellular sensitivity following Photofrin-mediated photodynamic therapy (PDT). Previously we reported that immortalized Li-Fraumeni syndrome (LFS) cells are more resistant to Photofrin-mediated PDT compared to normal human fibroblasts (NHF) at equivalent cellular Photofrin levels. In the current work we report that Photofrin-mediated PDT increased the activity of JNK1 and p38 within 30 min in both cell types. However, the increased activity of JNK1 and p38 was transient in the sensitive NHF cells and returned back to near basal levels by 3 h after PDT. In contrast, the resistant LFS cells exhibited a more prolonged activation of JNK and p38, which lasted for at least 11 h and 7 h after PDT, respectively. Blocking of the p38 pathway in LFS cells by transient infection with a recombinant adenovirus expressing a dominant negative mutant of p38 or in HeLa cells by stable transfection with a dominant negative mutant of p38 had no effect on cell survival following PDT. These data suggest that although Photofrin-mediated PDT is able to induce JNK1 and p38 in human cells, the p38 pathway alone does not play a major role in the sensitivity of LFS cells to Photofrin-mediated PDT.
Tong
Zhimin
Z
Department of Biology, McMaster University, Hamilton, ON, Canada L8S 4K1.
Singh
Gurmit
G
Valerie
Kristoffer
K
Rainbow
Andrew J
AJ
D015153:Blotting, Western; D002478:Cells, Cultured; D017323:Dihematoporphyrin Ether / Q000494:pharmacology*; D004789:Enzyme Activation; D004790:Enzyme Induction; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010778:Photochemotherapy; D048051:p38 Mitogen-Activated Protein Kinases
D017323:Dihematoporphyrin Ether; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases