Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts
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 inves...
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doaj-ba4c34d9356143279eb7e6a8c57c3cf02020-11-25T00:05:19ZengPortland Press, Biochemical SocietyBioscience Reports1573-49352015-03-01352e0018610.1042/BSR20140164BSR20140164Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblastsLi Sui0Rui‑Hong Zhang1Ping Zhang2Ke‑Li Yun3Hong‑Cai Zhang4Li Liu5Ming‑Xu Hu6 Department of Emergency Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China Department of Chinese 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 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 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.http://www.bioscirep.org/bsr/035/e186/bsr035e186.htmautophagycardiofibroblastsendoplasmic reticulum (ER) stresslead toxicitymammalian target of rapamycin (mTOR) pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li Sui Rui‑Hong Zhang Ping Zhang Ke‑Li Yun Hong‑Cai Zhang Li Liu Ming‑Xu Hu |
spellingShingle |
Li Sui Rui‑Hong Zhang Ping Zhang Ke‑Li Yun Hong‑Cai Zhang Li Liu Ming‑Xu Hu Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts Bioscience Reports autophagy cardiofibroblasts endoplasmic reticulum (ER) stress lead toxicity mammalian target of rapamycin (mTOR) pathway |
author_facet |
Li Sui Rui‑Hong Zhang Ping Zhang Ke‑Li Yun Hong‑Cai Zhang Li Liu Ming‑Xu Hu |
author_sort |
Li Sui |
title |
Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts |
title_short |
Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts |
title_full |
Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts |
title_fullStr |
Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts |
title_full_unstemmed |
Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts |
title_sort |
lead toxicity induces autophagy to protect against cell death through mtorc1 pathway in cardiofibroblasts |
publisher |
Portland Press, Biochemical Society |
series |
Bioscience Reports |
issn |
1573-4935 |
publishDate |
2015-03-01 |
description |
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. |
topic |
autophagy cardiofibroblasts endoplasmic reticulum (ER) stress lead toxicity mammalian target of rapamycin (mTOR) pathway |
url |
http://www.bioscirep.org/bsr/035/e186/bsr035e186.htm |
work_keys_str_mv |
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