Tong Zhimin, Singh Gurmit, Valerie Kristoffer, Rainbow Andrew J
Department of Biology, McMaster University, Hamilton, ON, Canada L8S 4K1.
J Photochem Photobiol B. 2003 Oct 15;71(1-3):77-85. doi: 10.1016/j.jphotobiol.2003.08.001.
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.
我们研究了应激激活的JNK和p38蛋白激酶在卟啉钠介导的光动力疗法（PDT）后细胞敏感性中的可能作用。此前我们报道，在同等细胞卟啉钠水平下，永生化的李-弗劳梅尼综合征（LFS）细胞比正常人成纤维细胞（NHF）对卟啉钠介导的PDT更具抗性。在当前研究中，我们报道卟啉钠介导的PDT在30分钟内增加了两种细胞类型中JNK1和p38的活性。然而，JNK1和p38活性的增加在敏感的NHF细胞中是短暂的，在PDT后3小时恢复到接近基础水平。相比之下，抗性的LFS细胞表现出JNK和p38的激活持续时间更长，分别在PDT后至少持续11小时和7小时。通过瞬时感染表达p38显性负突变体的重组腺病毒阻断LFS细胞中的p38途径，或通过稳定转染p38显性负突变体阻断HeLa细胞中的p38途径，对PDT后的细胞存活没有影响。这些数据表明，尽管卟啉钠介导的PDT能够在人类细胞中诱导JNK1和p38，但单独的p38途径在LFS细胞对卟啉钠介导的PDT的敏感性中并不起主要作用。
