Journal Article

Cadmium Decreases Gap Junctional Intercellular Communication in Mouse Liver

Sang-Hee Jeong, Sultan S. M. Habeebu and Curtis D. Klaassen ‡

in Toxicological Sciences

Volume 57, issue 1, pages 156-166
Published in print September 2000 | ISSN: 1096-6080
Published online September 2000 | e-ISSN: 1096-0929 | DOI:
Cadmium Decreases Gap Junctional Intercellular Communication in Mouse Liver

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Cadmium (Cd) is an environmental pollutant of increasing importance, due to industrialization, smoking, and the lack of effective therapy for Cd poisoning. The general population is exposed to Cd principally through food and water. The metal accumulates slowly in the liver and kidney, the target organs of acute and chronic Cd toxicity, respectively. We showed recently that liver is also a target organ for chronic Cd toxicity. Gap junctional intercellular communication (GJIC) is a means of maintaining cellular homeostasis in multicellular organisms. It involves the transfer of small, water-soluble molecules through intercellular channels (gap junctions), composed of proteins called connexins. The major connexins of liver (hepatocytes) are connexin 32 (Cx32) and connexin 26 (Cx26). Cd disrupts cellular homeostasis in the liver through its induction of necrosis, apoptosis, and cellular proliferation. 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 apoptosis and cell proliferation induced by Cd in vivo. Mice were injected ip with 30 μmol Cd/kg, and were observed for up to 48 h. Other groups of mice were injected with 5–60 μmol Cd/kg and observed for 9 h. Blood and liver were harvested and used for analysis of GJIC, connexin expression, cytoskeletal actin, serum enzymes, and liver pathology. Cd produced a time- and dose-dependent inhibition of GJIC in liver, along with parallel decreases in the expression of Cx32 and Cx26. Cd also produced disruption and loss of cytoskeletal actin in liver in a time- and dose-dependent manner. These observations are discussed in relation to the toxicity of Cd, and possible mechanisms of induction of the GJIC-related alterations are presented.

Keywords: cadmium (Cd); gap junctional intercellular communication (GJIC); connexins; cytoskeletal actin; necrosis; apoptosis; cellular proliferation

Journal Article.  6557 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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