Gap Junction Blockage Promotes Cadmium-induced Apoptosis in BRL 3A Derived from Buffalo Rat Liver Cells

Overview

Journal J Vet Sci

Specialty Veterinary Medicine

Date 2016 Apr 7

PMID 27051341

Citations 4

Authors

Di Hu

Hui Zou

Tao Han

Junze Xie

Nannan Dai

Liling Zhuo

Jianhong Gu

Jianchun Bian

Yan Yuan

Xuezhong Liu

Zongping Liu

Affiliations

Soon will be listed here.

Abstract

Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and elevated intracellular free Ca(2+) concentration, corresponding to a decrease in gap junctional intercellular communication. Gap junction blockage pretreatment with 18β-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial transmembrane electrical potential (Δψm). Additionally, GA was found to enhance ERK and p38 activation during Cd-induced activation of mitogen-activated protein kinases, but had no significant effect on JNK activation. Our results indicated the apoptosis-related proteins and the ERK and p38 signaling pathways may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A cells.

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