title: Mitochondria defects are involved in lead-acetate-induced adult hematopoietic stem cell decline.
abstract: Occupational high-grade lead exposure has been reduced in recent decades as a result of increased regulation. However, environmental lead exposure remains widespread, and is associated with severe toxicity implicated in human diseases. We performed oral intragastric administration of various dose lead acetate to adult Sprague Dawley rats to define the role of lead exposure in hematopoietic stem cells (HSCs) function, and to clarify its underlying mechanism. Lead acetate-exposed rats exhibited developmental abnormalities in myeloid and lymphoid lineages, and a significant decline in immune functions. It also showed HSCs functional decline associated with senescent phenotype with low grade lead acetate exposure or apoptotic phenotype with relative higher grade dose exposure. Mechanistic exploration showed a significant increase in reactive oxygen species (ROS) in the lead acetate-exposed CD90(+)CD45(-) compartment, which correlated with functional defects in cellular mitochondria. Furthermore, in vivo treatment with the antioxidant vitamin C led to reversion of the CD90(+)CD45(-) compartment functional decline. These results indicate that lead acetate perturbs the hematopoietic balance of adult HSCs, associated with cellular mitochondria defects, increased intracellular ROS generation.
authors: Chengdu Research Institute of Reproduction and Infertility, Chengdu Women and Children's Central Hospital, Chongqing Medical University, Chengdu, Sichuan 610091, China. Electronic address: laujun@msn.cn.
authors: Jun
authors: J
authors: Liu
authors: Institute of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. Electronic address: jiadaoyong@126.com.
authors: Dao-Yong
authors: DY
authors: Jia
authors: Department of Neonatology, The Children's Hospital of Soochow University, No. 303 Jingde Rd., Suzhou, Jiangsu 215003, China. Electronic address: szcai@suda.edu.cn.
authors: Shi-Zhong
authors: SZ
authors: Cai
authors: Institute of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. Electronic address: 476061955@qq.com.
authors: Cheng-Peng
authors: CP
authors: Li
authors: Institute of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. Electronic address: 471747033@qq.com.
authors: Meng-Si
authors: MS
authors: Zhang
authors: Institute of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. Electronic address: yan2007220370@163.com.
authors: Yan-Yan
authors: YY
authors: Zhang
authors: MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: yanchk@gmail.com.
authors: Chong-Huai
authors: CH
authors: Yan
authors: Institute of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. Electronic address: ypwangcq@aliyun.com.
authors: Ya-Ping
authors: YP
authors: Wang
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D019070:Cell Lineage; D002478:Cells, Cultured; D016922:Cellular Senescence; D004195:Disease Models, Animal; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007855:Lead Poisoning / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009942:Organometallic Compounds; D018384:Oxidative Stress; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism
chemical_list: D000975:Antioxidants; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens; C516771:Ptprc protein, rat; C008261:lead acetate
keywords: Apoptosis; Hematopoietic stem cell; Lead-acetate (PbAc); Mitochondria defect; Reactive oxygen species (ROS); Senescence