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

Abstract

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.

Antagonistic effects of selenium on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens

“…In H9c2 rat cardiomyoblasts, oxidative stress may suppress mTOR activity and promote autophagy [ 40 ]. In addition, previous study documented that Pb toxicity induced autophagy via the mTORC1 pathway in cardio fibroblasts [ 41 , 42 ]. In our study, the Pb treatment promoted the expressions of Beclin 1, Dynein, ATG 5, LC3-I, and LC3-II and inhibited the expression of the mTOR.…”

Restoration of autophagy by puerarin in lead‐exposed primary rat proximal tubular cells via regulating AMPK–mTOR signaling

“…By contrast, Lv et al and Sui et al reported that Pb exposure promoted autophagy in cultured osteoblasts and cardiofibroblasts, respectively. [7,8] Moreover, mTOR kinase is a critical regulator of autophagy, which stimulates protein synthesis and inhibits autophagy induction. [9] The main upstream regulator of mTOR in mammalian cells is 5ʹAMPactivated protein kinase (AMPK).…”

Ellagic acid restored lead-induced nephrotoxicity by anti-inflammatory, anti-apoptotic and free radical scavenging activities

“…In this current study, lead exposure was responsible for a significant increase in expression level of LC3B in renal tissues when compared to control group. EA treatment caused reduction in LC3B level and demonstrated an anti-autophagic effect [ 28 ].…”