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PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway Free
Chenggang Li1,+, Haolin Liu1,+, Yang Sun1,+, 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,*
1State 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
2National 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
3Molecular Parasitology Laboratory, Department of Etiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China
4Department of Biological Science and Medical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College; Beijing 100005, China
5Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China
6Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China *Correspondence to:Chengyu Jiang, Tel: 10-65296908; Fax: 10-65276551; E-mail: jiang@pumc.edu.cn; Heng Wang, E-mail: hengwang@pumc.edu.cn; Haiyan Xu, E-mail: xuhy@pumc.edu.cn
J Mol Cell Biol, Volume 1, Issue 1, October 2009, 37-45,  https://doi.org/10.1093/jmcb/mjp002
Keyword: PAMAM nanoparticles; autophagy; acute lung injury; Akt; TSC2; mTOR
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.

Volume 1, Issue 1
October 2009