Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

Zou, Hui; Zhuo, Lang; Han, Tao; Hu, Di; Yang, Xiaolin; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Zongping

doi:10.1016/j.bbrc.2015.03.027

Cited by 56 publications

(30 citation statements)

References 36 publications

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“…Therefore, we explored the possibility that autophagy may be activated as a protective mechanism in response to Cd treatment. We have previously shown that autophagy plays a protective role during Cd-induced apoptosis in BRL 3 A cells for a 6 h duration 33 and in PC-12 cells for a 24 h duration 34 . According to our preliminary results, autophagy was activated from 2 to 18 h, and reached its peak after rPT cells were exposed to Cd for 6 h; this is in accord with our previous result in BRL 3A cells.…”

Section: Discussionmentioning

confidence: 97%

Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture

Liu

Yuan

Long

et al. 2017

Sci Rep

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The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was accompanied by simultaneous activation of autophagy resulted in reduced apoptosis. In this model, we induced autophagy through RAPA and further demonstrated that autophagy protects against activation of Fas/FasL signaling and apoptosis. The antiapoptotic effect of autophagy was blocked by 3-MA, an autophagy inhibitor. The interactions between Beclin-1 and Fas, FasL, FADD, caspase-8 and BID/tBID were relatively weak, with the exception of cleaved caspase-8, indicated that minimal interactions between these proteins and Beclin-1 are involved in maintaining the balance of autophagy and apoptosis. Beclin-1 precipitated with cleaved caspase-8 in a dose-dependent mannter, and the expression was increased by siRNA against Beclin-1. These data suggested that Beclin-1-mediated autophagy impairs the expression and function of cleaved caspase-8 to protect against Cd-induced activation of apopotosis through Fas/FasL signaling pathway.

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Section: Discussionmentioning

confidence: 97%

Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture

Liu

Yuan

Long

et al. 2017

Sci Rep

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“…Cadmium (Cd) is a toxic heavy metal found widely in nature, and diseases caused by Cd poisoning result in serious economic losses worldwide 23, 24 . The toxicity mechanism of Cd has been reported in many kinds of cells and animal experiments 25, 26 ; however, the mechanism of Cd damage to the kidneys is unclear.…”

Section: Discussionmentioning

confidence: 99%

PARP-1 overexpression contributes to Cadmium-induced death in rat proximal tubular cells via parthanatos and the MAPK signalling pathway

Luo

Yuan

et al. 2017

Sci Rep

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Parthanatos is a newly discovered form of PARP-1-dependent programmed cell death. It has been reported to play an important role in several cancer or tumour cells; however, few studies have been performed in normal cells. Cadmium is a highly toxic pollutant and is reported to induce autophagy and apoptosis in multiple cell types. Although cadmium toxicity induces cell death, the underlying mechanism is not fully understood. Therefore, in this study we aimed to investigate the mechanism of Cadmium -induced cell damage using rat proximal tubular cell line NRK-52E and primary rat proximal tubular (rPT) cells. Our results indicated that parthanatos and the MAPK signalling pathway contribute to Cadmium-induced cell death, and that oxidative stress and mitochondrial damage play key roles in this process. In addition, parthanatos with oxidative stress has a synergistic effect on apoptosis, and JNK1/2 and p38 contribute to parthanatos.

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“…For example, one study found that exposure of rat lung epithelial cells to carbon black and silica particles induced loss of GJIC and delocalization of Cx43 (Ale-Agha et al 2010 ). Furthermore, in rat liver cells, inhibition of GJIC and autophagy were involved in cadmium-induced apoptosis (Zou et al 2015 ). These studies have further shown that Cx43 is responsible for the decrease in GJIC.…”

Section: Discussionmentioning

confidence: 99%

Effects of carbon nanotubes on intercellular communication and involvement of IL-1 genes

Arnoldussen

Anmarkrud

Skaug

et al. 2016

J. Cell Commun. Signal.

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An increasing amount of products containing engineered nanoparticles is emerging. Among these particles are carbon nanotubes (CNTs) which are of interest for a wide range of industrial and biomedical applications. There have been raised concerns over the effects of CNTs on human health. Some types of CNTs are classified as group 2B carcinogens by the International Agency for Research on Cancer. CNTs may also induce pulmonary inflammatory and fibrotic effects. By utilizing CNTs of different lengths, we investigated the role of the proinflammatory cytokine, interleukin-1 (IL-1) on gap junctional intercellular communication (GJIC) by using IL-1 wild-type (IL1-WT) and IL-1 knock-out (IL1-KO) cells. GJIC decreased equally in both cell types after CNT exposure. Immunofluorescence staining showed Gja1 and Gjb2 in gap junctions and hemichannels for both cell types. Gjb1 and Gjb2 expression was low in IL1-KO cells, which was confirmed by protein analysis. Gja1 was upregulated with both CNTs, whereas Gjb1 was down-regulated by CNT-2 in IL1-WT cells. Connexin mRNA expression was regulated differently by the CNTs. CNT-1 affected Gja1 and Gjb2, whereas CNT-2 had an effect on Gjb1. CNTs negatively affect GJIC through gap junctions independently of the length of CNT and IL-1 status. Furthermore, connexin gene expression was affected by IL-1 at transcriptional and translational levels. As both CNTs used in this study are cytotoxic to the cells and reduce cell survival, we suggest that CNT-induced reduction in GJIC may be important for inhibiting transfer of cell survival signals between cells.Electronic supplementary materialThe online version of this article (doi:10.1007/s12079-016-0323-0) contains supplementary material, which is available to authorized users.

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Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

Cited by 56 publications

References 36 publications

Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture

Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture

PARP-1 overexpression contributes to Cadmium-induced death in rat proximal tubular cells via parthanatos and the MAPK signalling pathway

Effects of carbon nanotubes on intercellular communication and involvement of IL-1 genes

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