title: Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts.
abstract: Heavy metals, such as lead (Pb(2+)), are usually accumulated in human bodies and impair human's health. Lead is a metal with many recognized adverse health side effects and yet the molecular processes underlying lead toxicity are still poorly understood. In the present study, we proposed to investigate the effects of lead toxicity in cultured cardiofibroblasts. After lead treatment, cultured cardiofibroblasts showed severe endoplasmic reticulum (ER) stress. However, the lead-treated cardiofibroblasts were not dramatically apoptotic. Further, we found that these cells determined to undergo autophagy through inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway. Moreover, inhibition of autophagy by 3-methyladenine (3-MA) may dramatically enhance lead toxicity in cardiofibroblasts and cause cell death. Our data establish that lead toxicity induces cell stress in cardiofibroblasts and protective autophagy is activated by inhibition of mTORC1 pathway. These findings describe a mechanism by which lead toxicity may promote the autophagy of cardiofibroblasts cells, which protects cells from cell stress. Our findings provide evidence that autophagy may help cells to survive under ER stress conditions in cardiofibroblasts and may set up an effective therapeutic strategy for heavy metal toxicity.
authors: *Department of Emergency Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors: Li
authors: L
authors: Sui
authors: †Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors: Rui-Hong
authors: RH
authors: Zhang
authors: ‡Department of Chinese Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors: Ping
authors: P
authors: Zhang
authors: §School of Food Science and Engineering, Harbin Institute of Technology, Harbin 150090, China.
authors: Ke-Li
authors: KL
authors: Yun
authors: ║Academy of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors: Hong-Cai
authors: HC
authors: Zhang
authors: ¶Department of Cardiology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors: Li
authors: L
authors: Liu
authors: ‡Department of Chinese Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors: Ming-Xu
authors: MX
authors: Hu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007854:Lead / Q000633:toxicity*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases
chemical_list: D046912:Multiprotein Complexes; D007854:Lead; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases