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

被引：20

作者：

Zhou, Cuihong ^{[1
,2
]}

Zhou, Jun ^{[1
,2
]}

Sheng, Fugeng ^{[3
]}

Zhu, Haichuan ^{[4
]}

Deng, Xiaoyan ^{[1
]}

Xia, Bin ^{[2
]}

Lin, Jian ^{[2
]}

机构：

[1] Beihang Univ, Minist Educ, Sch Biol Sci & Biomed Engn, Key Lab Biomech & Mechanobiol, Beijing 100191, Peoples R China

[2] Peking Univ, Coll Chem & Mol Engn, Inst Analyt Chem, Beijing Nucl Magnet Resonance Ctr, Beijing 100871, Peoples R China

[3] Acad Mil Med Sci, Affiliated Hosp, Dept Radiol, Beijing 100071, Peoples R China

[4] Hubei Univ, Coll Life Sci, Wuhan 430072, Peoples R China

来源：

ACTA BIOCHIMICA ET BIOPHYSICA SINICA | 2012年 / 44卷 / 10期

基金：

中国国家自然科学基金;

关键词：

ZnPPIX; autophagy; Beclin1-independent autophagy; p38; ZINC PROTOPORPHYRIN; CELL-DEATH; STRESS;

D O I：

10.1093/abbs/gms064

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：815 / 822

页数：8

共 19 条

[11] Non-canonical autophagy [J].

Scarlatti, Francesca ;

Maffei, Roberta ;

Beau, Isabelle ;

Ghidoni, Riccardo ;

Codogno, Patrice .

AUTOPHAGY, 2008, 4 (08) :1083-1085

[12] Rapamycin Promotes Autophagy and Reduces Neural Tissue Damage and Locomotor Impairment after Spinal Cord Injury in Mice [J].

Sekiguchi, Akira ;

Kanno, Haruo ;

Ozawa, Hiroshi ;

Yamaya, Seiji ;

Itoi, Eiji .

JOURNAL OF NEUROTRAUMA, 2012, 29 (05) :946-956

[13] Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells [J].

Smith, D. M. ;

Patel, S. ;

Raffoul, F. ;

Haller, E. ;

Mills, G. B. ;

Nanjundan, M. .

CELL DEATH AND DIFFERENTIATION, 2010, 17 (12) :1867-1881

[14] Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18 [J].

Tian, Songhai ;

Lin, Jian ;

Zhou, Jun ;

Wang, Xiaolong ;

Li, Yanjun ;

Ren, Xiaobai ;

Yu, Wenyu ;

Zhong, Wu ;

Xiao, Junhai ;

Sheng, Fugeng ;

Chen, Yingyu ;

Jin, Changwen ;

Li, Song ;

Zheng, Zhibing ;

Xia, Bin .

AUTOPHAGY, 2010, 6 (08) :1032-1041

[15] Heme Oxygenase-1 in Tumor Biology and Therapy [J].

Was, Halina ;

Dulak, Jozef ;

Jozkowicz, Alicja .

CURRENT DRUG TARGETS, 2010, 11 (12) :1551-1570

[16] Unique effects of zinc protoporphyrin on HO-1 induction and apoptosis [J].

Yang, G ;

Nguyen, X ;

Ou, J ;

Rekulapelli, P ;

Stevenson, DK ;

Dennery, PA .

BLOOD, 2001, 97 (05) :1306-1313

[17] Inhibition of Heme Oxygenase-1 Enhances the Radiosensitivity in Human Nonsmall Cell Lung Cancer A549 Cells [J].

Zhang, Wenyi ;

Qiao, Tiankui ;

Zha, Lin .

CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 2011, 26 (05) :639-645

[18] Monitoring autophagic flux by an improved tandem fluorescent-tagged LC3 (mTagRFP-mWasabi-LC3) reveals that high-dose rapamycin impairs autophagic flux in cancer cells [J].

Zhou, Cuihong ;

Zhong, Wu ;

Zhou, Jun ;

Sheng, Fugeng ;

Fang, Ziyuan ;

Wei, Yue ;

Chen, Yingyu ;

Deng, Xiaoyan ;

Xia, Bin ;

Lin, Jian .

AUTOPHAGY, 2012, 8 (08) :1215-1226

[19] Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death [J].

Zhu, Jian-hui ;

Horbinski, Craig ;

Guo, Fengli ;

Watkins, Simon ;

Uchiyama, Yasuo ;

Chu, Charleen T. .

AMERICAN JOURNAL OF PATHOLOGY, 2007, 170 (01) :75-86

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