Chronic lithium administration triggers an over-expression of GRP94 stress protein isoforms in mouse liver

Moderate doses of lithium were chronically administered to mice in order to verify whether the cytoprotective effects of lithium could be in part attributed to a molecular protection conferred by stress proteins/chaperones accumulation. In order to reach serum lithium levels within the common therapeutic values, mice were fed for 6 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.5 and 0.9 mM Li, respectively. Under these experimental conditions, no clinical side-effects were observed. Urea and creatinine concentrations in serum, lipids peroxidation level and activities of catalase, superoxide-dismutase and glutathione-peroxidase in liver and kidney were not significantly different from control values. Although the expression level of the constitutive HSP73 was not significantly modified, HSP72 was found to be down-regulated in kidney after 1 month. In liver, three protein bands were immunodetected by the anti-GRP94 antibody: 98 kDa and 96 kDa proteins corresponding to more or less glycosylated forms and/or phosphorylated forms of GRP94 and a 80 kDa protein probably being a cleavage product of GRP94. The 96 kDa and 80 kDa proteins were significantly up-regulated in liver of lithium-treated mice as compared to controls.