Gap Junction Intercellular Communication Negatively Regulates Cadmium-Induced Autophagy and Inhibition of Autophagic Flux in Buffalo Rat Liver 3A Cells.

Hui Zou,Jianchun Bian,Tao Wang,Junzhao Yuan,Zongping Liu,Yan Yuan,Yan Chen,Yi Zhang

doi:10.3389/fphar.2020.596046

Abstract

Cadmium is an important environmental pollutant that poses a serious threat to the health of humans and animals. A large number of studies have shown that the liver is one of the important target organs of cadmium. Stimulation of cells can lead to rapid changes in gap junction intercellular communication (GJIC) and autophagy. Previous studies have shown that cadmium can inhibit GJIC and induce autophagy. In order to understand the dynamic changes of GJIC and autophagy in the process of cadmium-induced hepatotoxic injury and the effects of GJIC on autophagy, a time-gradient model of cadmium cytotoxicity was established. The results showed that within 24 h of cadmium exposure, 5 μmol/L cadmium inhibited GJIC by down regulating the expression levels of connexin 43 (Cx43) and disturbing the localization of Cx43 in Buffalo rat liver 3A (BRL 3A) cells. In addition, cadmium induced autophagy and then inhibited autophagic flux in the later stage. During this process, inhibiting of GJIC could exacerbate the cytotoxic damage of cadmium and induce autophagy, but further blocked autophagic flux, promoting GJIC in order to obtain the opposite results.

Highlights

Cadmium (Cd) is a significant pollutant caused by the improper emissions in the industry
We further found that Cd treatment increased the levels of Ca2+ in the cytoplasm, which is the main reason for the induction of hepatotoxicity and apoptosis in the Buffalo rat liver 3A (BRL 3A) cell line (Zou et al, 2015b).it is an indisputable fact that Cd exposure causes decreased gap junction intercellular communication (GJIC) function and reduced connexins expression
We further showed that Cd triggered autophagy in a dosedependent manner and that autophagy exerted a protective effect on the cytotoxicity of Cd in BRL 3A cells (Zou et al, 2015c)

Summary

Introduction

Cadmium (Cd) is a significant pollutant caused by the improper emissions in the industry. It is difficult for animals and humans to excrete Cd as it can be present in the body for as long as 30 years (Nordberg, 2009). The amount that Cd stored in the liver is approximately one third of the total amount of the whole body (Marettova et al, 2012). The role of the liver in animal metabolism and energy distribution is crucial, and the function of hepatocytes is greatly dependent on autophagy. It has been shown that hepatocytes maintain at a basic level of autophagy and that the fluctuation of autophagy levels can largely affect their physiological functions. The changes in the function of autophagy are closely associated

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Results

Conclusion