Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts

Bioscience Reports

Rui‑Hong Zhang¹  Li Liu²  Ping Zhang³  Ming‑Xu Hu³  Li Sui⁴  Ke‑Li Yun⁵  Hong‑Cai Zhang⁶ 

[1] Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;Department of Cardiology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China;Department of Chinese Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;Department of Emergency Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;School of Food Science and Engineering, Harbin Institute of Technology, Harbin 150090, China;║Academy of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China;

关键词: autophagy;    cardiofibroblasts;    endoplasmic reticulum (ER) stress;    lead toxicity;    mammalian target of rapamycin (mTOR) pathway;   

DOI  :  10.1042/BSR20140164

来源: DOAJ

【 摘 要 】

Heavy metals, such as lead (Pb2+), 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.

【 授权许可】

Unknown