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首页> 外文期刊>Oncogene >p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative
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p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative

机译：p38 MAPK在新型乙二醇卟啉衍生物的光活化诱导的细胞凋亡中起重要作用

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In this study, we provide evidence that photostimulation of various cancer cells preloaded with a new photosensitizing compound, tetrakis-meso-(4-ethyleneglycol-2,3,5,6-tetrafluorophenyl) porphyrin (PORF-TEG), results in rapid activation of the cell death machinery. PORF-TEG, although primarily localized in lysosomes, induces mitochondria-driven apoptosis. The induction of apoptosis is accompanied by immediate and sustained activation of p38 mitogen-activated protein kinase (MAPK) and transient activation of c-Jun N-terminal kinase (JNK). Conversely, the inhibition of p38 by PD 169316 or SB202190 and by the p38α dominant-negative mutant as well as the deletion of the p38α gene (MEFs-KO) protected cells from apoptosis, whereas inhibition of JNK did not. Activation of the p38 signaling pathway occurs upstream of caspase activation. In addition, preincubation of cells with scavengers of reactive oxygen species attenuated p38 and caspase activation and increased cell survival, thus connecting reactive oxygen species formation with the activation of the p38 pathway. Later events included degradation of Bcl-2, activation of tBid, and cleavage of Bad and Mcl-1. The data suggest a key role for p38 MAPK in PORF-TEG-photoinduced apoptosis.
机译：在这项研究中，我们提供的证据表明，预先装有新的光敏化合物四-中-（4-乙二醇-2,3,5,6-四氟苯基）卟啉（PORF-TEG）的各种癌细胞的光刺激会导致快速激活细胞死亡机制。 PORF-TEG虽然主要位于溶酶体中，但诱导线粒体驱动的细胞凋亡。凋亡的诱导伴随着p38丝裂原活化蛋白激酶（MAPK）的即时和持续活化以及c-Jun N末端激酶（JNK）的瞬时活化。相反，PD 169316或SB202190以及p38α显性阴性突变体对p38的抑制以及p38α基因（MEFs-KO）的缺失可保护细胞免于凋亡，而JNK的抑制则不会。 p38信号通路的激活发生在caspase激活的上游。此外，将细胞与活性氧清除剂进行预孵育会减弱p38和caspase的活化并提高细胞存活率，从而将活性氧的形成与p38途径的活化联系起来。后来的事件包括Bcl-2的降解，tBid的激活以及Bad和Mcl-1的裂解。数据表明p38 MAPK在PORF-TEG光诱导的细胞凋亡中起关键作用。

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