The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1-independent, autophagy through p38 MAPK pathway.
The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1-independent, autophagy through p38 MAPK pathway.
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DOI：
10.1093/abbs/gms064
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发表时间：
2012-10
影响因子：
3.7
通讯作者：
C. Zhou;Jun Zhou;Fugeng Sheng;Haichuan Zhu;Xiaoyan Deng;Bin Xia;Jian Lin
中科院分区：
文献类型：
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作者：
C. Zhou;Jun Zhou;Fugeng Sheng;Haichuan Zhu;Xiaoyan Deng;Bin Xia;Jian Lin
原卟啉锌IX （Zinc protoporphyrin IX, ZnPPIX）是一种血红素加氧酶-1酶抑制剂，具有诱导细胞凋亡和抗肿瘤的作用。在这里，我们报道了ZnPPIX在HeLa细胞中触发自噬并导致缺陷的自噬通量。自噬体的形成不依赖于Beclin 1，表明znppix处理的细胞具有非典型自噬活性。此外，western blot结果显示p38 MAPK（丝裂原活化蛋白激酶）在处理细胞中磷酸化。同样，SB203580（一种p38抑制剂）明显抑制自噬体的积累。我们的研究结果表明p38 MAPK可能是非典型beclin1非依赖性自噬的关键调节因子。
Zinc protoporphyrin IX (ZnPPIX), a heme oxygenase-1 enzyme inhibitor, has been reported to induce apoptosis and to have antitumor properties. Here, we report that ZnPPIX triggers autophagy and causes defective autophagy flux in HeLa cells. Autophagosome formation was independent of Beclin 1, indicating non-canonical autophagy activity in ZnPPIX-treated cells. Furthermore, western blot results indicated that p38 MAPK (mitogen-activated protein kinase) was phosphorylated in treated cells. Consistently, SB203580 (a p38 inhibitor) obviously inhibited the accumulation of autophagosomes. Our results indicated that p38 MAPK may be a key regulator for non-canonical Beclin1-independent autophagy.