The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1-independent, autophagy through p38 MAPK pathway

Cuihong Zhou; Jun Zhou; Fugeng Sheng; Haichuan Zhu; Xiaoyan Deng; Bin Xia; Jian Lin

doi:10.1093/abbs/gms064

The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1-independent, autophagy through p38 MAPK pathway

Acta Biochim Biophys Sin (Shanghai). 2012 Oct;44(10):815-22. doi: 10.1093/abbs/gms064. Epub 2012 Aug 7.

Authors

Cuihong Zhou¹, Jun Zhou, Fugeng Sheng, Haichuan Zhu, Xiaoyan Deng, Bin Xia, Jian Lin

Affiliation

¹ Key Laboratory for Biomechanics and Mechanobiology of the Ministry of Education, School of Biological Sciences and Biomedical Engineering, Beihang University, Beijing, China.

PMID: 22875631
DOI: 10.1093/abbs/gms064

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism*
Autophagy / drug effects*
Beclin-1
Blotting, Western
Cell Survival / drug effects
Enzyme Inhibitors / pharmacology
Gene Knockdown Techniques
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
HeLa Cells
Heme Oxygenase-1 / antagonists & inhibitors
Heme Oxygenase-1 / metabolism
Humans
Imidazoles / pharmacology
MAP Kinase Signaling System / drug effects*
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Microscopy, Confocal
Microscopy, Electron, Transmission
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism
Phagosomes / drug effects
Phagosomes / metabolism
Phagosomes / ultrastructure
Phosphorylation / drug effects
Protoporphyrins / pharmacology*
Pyridines / pharmacology
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Apoptosis Regulatory Proteins
BECN1 protein, human
Beclin-1
Enzyme Inhibitors
Imidazoles
MAP1LC3A protein, human
Membrane Proteins
Microtubule-Associated Proteins
Protoporphyrins
Pyridines
Green Fluorescent Proteins
zinc protoporphyrin
Heme Oxygenase-1
p38 Mitogen-Activated Protein Kinases
SB 203580