Cadmium decreases gap junctional intercellular communication in mouse liver

Cadmium (Cd) is an environmental pollutant of increasing importance, due to industrialization, smoking, and the lack of effective therapy for Cd poiso ning. The general population is exposed to Cd principally through food and water. The metal accumulates slowly in the liver and kidney, the target org ans of acute and chronic Cd toxicity, respectively. We showed recently that liver is also a target organ for chronic Cd toxicity. Gap junctional inter cellular communication (GJIC) is a means of maintaining cellular homeostasi s in multicellular organisms. It involves the transfer of small, water-solu ble molecules through intercellular channels (gap junctions), composed of p roteins called connexins. The major connexins of liver (hepatocytes) are co nnexin 32 (Cx32) and connexin 26 (Cx26). Cd disrupts cellular homeostasis i n the liver through its induction of necrosis, apoptosis, and cellular prol iferation. It is to be expected, therefore, that Cd must exert some effect on GJIC, This study investigates Cd-induced alterations in GJIC, Cx32, and Cx26 expression, and in cytoskeletal actin, and relates the changes to apop tosis and cell proliferation induced by Cd in vivo. Mice were injected ip w ith 30 mu mol Cd/kg, and were observed for up to 48 h, Other groups of mice were injected with 5-60 mu mol Cd/kg and observed for 9 h. Blood and liver were harvested and used for analysis of GJIC, connexin expression, cytoske letal actin, serum enzymes, and liver pathology, Cd produced a time- and do se-dependent inhibition of GJIC in liver, along with parallel decreases in the expression of Cx32 and Cx26. Cd also produced disruption and loss of cy toskeletal actin in liver in a time- and dose-dependent manner. These obser vations are discussed in relation to the toxicity of Cd, and possible mecha nisms of induction of the GJIC-related alterations are presented.