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Journal of Molecular Cell Biology Advance Access first published online on June 10, 2009
This version published online on July 2, 2009
Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjp002
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© The Author (2009). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

PAMAM Nanoparticles Promote Acute Lung Injury by Inducing Autophagic Cell Death through the Akt-TSC2-mTOR Signaling Pathway

Chenggang Li1,{dagger}, Haolin Liu1,{dagger}, Yang Sun1,{dagger}, Hongliang Wang1, Feng Guo1, Shuan Rao1, Jiejie Deng1, Yanli Zhang1, Yufa Miao2, Chenying Guo3, Jie Meng4, Xiping Chen5, Limin Li5, Dangsheng Li6, Haiyan Xu4,*, Heng Wang3,*, Bo Li2 and Chengyu Jiang1,*

1 State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College; Beijing 100005, China
2 National Center for Safety Evaluation of Drugs, National Institute for the Control of Pharmaceutical and Biological Products, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing 100176, China
3 Molecular Parasitology Laboratory, Department of Etiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China
4 Department of Biological Science and Medical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College; Beijing 100005, China
5 Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China
6 Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

* Correspondence to: Chengyu Jiang, Tel: 10-65296908; Fax: 10-65276551; E-mail: jiang{at}pumc.edu.cn. Heng Wang, E-mail: hengwang{at}pumc.edu.cn. Haiyan Xu, E-mail: xuhy{at}pumc.edu.cn


  Abstract

Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011–2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

Keywords: PAMAM, nanoparticles, autophagy, acute lung injury, Akt, TSC2, mTOR

Received February 10, 2009; Revised April 14, 2009; Accepted April 16, 2009

{dagger} These authors contributed equally to this work.

In the original published version of this article, the corresponding authors were given in the wrong order. The publisher wishes to apologize for this error.


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M. Liu, H. Zhang, and A. S. Slutsky
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J Mol Cell Biol, October 1, 2009; 1(1): 6 - 7.
[Abstract] [Full Text] [PDF]


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