title: The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1-independent, autophagy through p38 MAPK pathway.
abstract: 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.
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of the Ministry of Education, School of Biological Sciences and Biomedical Engineering, Beihang University, Beijing, China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Fugeng
authors.initials: F
authors.lastname: Sheng
authors.forename: Haichuan
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.forename: Bin
authors.initials: B
authors.lastname: Xia
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D004791:Enzyme Inhibitors; D007093:Imidazoles; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011524:Protoporphyrins; D011725:Pyridines; D049452:Green Fluorescent Proteins; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580