title: Gap junction blockage promotes cadmium-induced apoptosis in BRL 3A derived from Buffalo rat liver cells.
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.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Hu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Junze
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Dai
authors.affiliation: Department of Life Science, Zaozhuang College, Zaozhuang 277160, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Zhuo
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Bian
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Zongping
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018031:Connexin 43; D002104:Cadmium; D002118:Calcium
keywords: BRL 3A cells; apoptosis; cadmium; gap junction blockage