Effect of Chronic Ethanol Exposure on Inositol Trisphosphate Receptors in WB Rat Liver Epithelial Cells

Abstract

We propose that the enhanced agonist-mediated Ca2+ mobilization observed in chronic ethanol-treated WB liver epithelial cells results from increased IP3R expression caused by an inhibition of IP3R degradation pathways by ethanol.

Chronic EtOH administration alters liver Mg2+homeostasis

“…Extensive investigation in various experimental models and alcoholic patients (1,14,28,52) indicates that chronic EtOH consumption alters physiological functions and ion pattern within several tissues. Tissue Na ϩ and Ca 2ϩ content have been reported to increase as a result of an altered operation of transport mechanisms (15,48) and cell signaling (2,21,22). A decrease in tissue Mg 2ϩ content has also been reported to occur in brain, heart, and other tissues, but the causes for this decrease still remain largely unclear.…”

Tumor Necrosis Factor-α Potentiates Intraneuronal Ca2+ Signaling via Regulation of the Inositol 1,4,5-Trisphosphate Receptor

“…Nevertheless, the Ca 2ϩ signal enhancement temporally correlated with increased IP 3 R protein levels, and changes in steadystate levels of IP 3 R protein have been shown previously to directly alter Ca 2ϩ responses without additional modifications to the receptor (37,38).…”

Ethanol and Lipid Metabolic Signaling

“…Preliminary evidence suggests that the enhanced action of IP3R reflects a potentiation of the Ca 2ϩ stimulatory phase of the protein, without a significant change in IP3R protein levels. Interestingly, in parallel studies, Bokkala et al (1999) described an enhancement of IP3R-mediated Ca 2ϩ release in WB cells (an epithelial cell line from Fischer-344 rat liver) by chronic ethanol treatment in vitro, which was entirely due to change in IP3R protein level. Surprisingly, PLC␥ activation by tyrosine kinase receptors in rat hepatocytes shows a markedly different pattern of changes after chronic ethanol feeding.…”