4.6 Article

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

Journal

BIOSCIENCE REPORTS
Volume 35, Issue -, Pages -

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BSR20140164

Keywords

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

Funding

  1. Ministry open topic for myocardial ischaemia Key Laboratory [KF201207]
  2. Chinese medicine research programme of Heilongjiang Province [ZHY12-Z111]

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available