Klotz L O, Fritsch C, Briviba K, Tsacmacidis N, Schliess F, Sies H
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Cancer Res. 1998 Oct 1;58(19):4297-300.
5-Aminolevulinate (ALA) photodynamic therapy (PDT) is being used clinically for the treatment of skin cancers. ALA is applied as a precursor of porphyrins serving as endogenous photosensitizers. Irradiation of HaCaT cells preincubated with 1 mM ALA for 24 h with red light of 570-750 nm at a dose of 4.5 J/cm2 leads to a 6-fold elevation of cellular c-Jun N-terminal kinase activity; phosphorylation of p38 mitogen-activated protein kinase (MAPK) is enhanced to a similar extent. In contrast, neither activation nor increased phosphorylation of the extracellular stimulus-regulated kinase MAPKs is detected. p38 is also phosphorylated by ALA-PDT in the human melanoma cell lines Bro and SkMel-23, applying doses that lead to 80-95% cell death after 24 h. Hence, the effects of ALA-PDT on MAPKs are similar to stresses like UV irradiation or exposure to hydrogen peroxide with respect to activation of JNK and p38 MAPKs. They are different, however, in that extracellular stimulus-regulated kinase activity is not raised by ALA-PDT. Of the 830 pmol porphyrins/mg protein that were present at 24 h in HaCaT cells, 99 pmol/mg were intracellular. When extracellular porphyrins had been removed by washing, p38 responses were retained. Thus, intracellular porphyrins synthesized from ALA are sufficient to elicit activation of p38 on photosensitization.
5-氨基酮戊酸（ALA）光动力疗法（PDT）正在临床上用于治疗皮肤癌。ALA作为卟啉的前体被应用，卟啉作为内源性光敏剂。用1 mM ALA预孵育24小时的HaCaT细胞，以4.5 J/cm²的剂量用570 - 750 nm的红光照射，会导致细胞c-Jun N端激酶活性升高6倍；p38丝裂原活化蛋白激酶（MAPK）的磷酸化程度也有类似增强。相比之下，未检测到细胞外信号调节激酶MAPKs的激活或磷酸化增加。在人黑色素瘤细胞系Bro和SkMel-23中，ALA-PDT也会使p38磷酸化，施加的剂量在24小时后会导致80 - 95%的细胞死亡。因此，就JNK和p38 MAPKs的激活而言，ALA-PDT对MAPKs的影响类似于紫外线照射或过氧化氢暴露等应激。然而，不同的是，ALA-PDT不会提高细胞外信号调节激酶的活性。在HaCaT细胞中，24小时时存在830 pmol卟啉/毫克蛋白，其中99 pmol/毫克是细胞内的。当通过洗涤去除细胞外卟啉后，p38反应仍会保留。因此，由ALA合成的细胞内卟啉足以在光致敏时引发p38的激活。
