title: Ambient Fine Particulate Matter Suppresses In Vivo Proliferation of Bone Marrow Stem Cells through Reactive Oxygen Species Formation.
abstract: OBJECTIVE
  Some environmental insults, such as fine particulate matter (PM) exposure, significantly impair the function of stem cells. However, it is unknown if PM exposure could affect the population of bone marrow stem cells (BMSCs). The present study was to investigate the effects of PM on BMSCs population and related mechanism(s).
  PM was intranasally distilled into male C57BL/6 mice for one month. Flow cytometry with antibodies for BMSCs, Annexin V and BrdU ware used to determine the number of BMSCs and the levels of their apoptosis and proliferation in vivo. Phosphorylated Akt (P-Akt) level was determined in the BM cells with western blotting. Intracellular reactive oxygen species (ROS) formation was quantified using flow cytometry analysis. To determine the role of PM-induced ROS in BMSCs population, proliferation, and apotosis, experiments were repeated using N-acetylcysteine (NAC)-treated wild type mice or a triple transgenic mouse line with overexpression of antioxidant network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase-1 with decreased in vivo ROS production.
  
  
  RESULTS
  PM treatment significantly reduced BMSCs population in association with increased ROS formation, decreased P-Akt level, and inhibition of proliferation of BMSCs without induction of apoptosis. NAC treatment or AON overexpression with reduced ROS formation effectively prevented PM-induced reduction of BMSCs population and proliferation with partial recovery of P-Akt level.
  
  
  CONCLUSIONS
  PM exposure significantly decreased the population of BMSCs due to diminished proliferation via ROS-mediated mechanism (could be partially via inhibition of Akt signaling).
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America; Department of Cardiology, Shandong Provincial Hospital, Shandong University, 324 Jing 5 road, Jinan, Shandong 250021, P.R. China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America; Department of Cardiovascular Medicine, the First Affiliated Hospital,Chongqing Medical University, Chongqing 400016, China.
authors.forename: Fengpeng
authors.initials: F
authors.lastname: Jia
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: He
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xie
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Minghuan
authors.initials: M
authors.lastname: Fu
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Hao
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Dylan Z
authors.initials: DZ
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Melbourne, St. Vincent's Hospital, Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America; Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation / Q000187:drug effects; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D000111:Acetylcysteine