Gap junction blockage promotes cadmium-induced apoptosis in BRL 3A derived from Buffalo rat liver cells.
- Author:
Di HU
1
;
Hui ZOU
;
Tao HAN
;
Junze XIE
;
Nannan DAI
;
Liling ZHUO
;
Jianhong GU
;
Jianchun BIAN
;
Yan YUAN
;
Xuezhong LIU
;
Zongping LIU
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: BRL 3A cells; apoptosis; cadmium; gap junction blockage
- MeSH: Animals; Apoptosis/*drug effects; Cadmium/*toxicity; Calcium/metabolism; Cell Communication/drug effects; Connexin 43/genetics; Enzyme Activation/drug effects; Gap Junctions/*drug effects; Gene Expression Regulation/drug effects; Hepatocytes/cytology/*drug effects; Rats; Signal Transduction/drug effects
- From:Journal of Veterinary Science 2016;17(1):63-70
- CountryRepublic of Korea
- Language:English
- 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 Ca2+ 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.
