tailieunhanh - Báo cáo khoa học: Lithium increases PGC-1a expression and mitochondrial biogenesis in primary bovine aortic endothelial cells

Lithium is a therapeutic agent commonly used to treat bipolar disorder and its beneficial effects are thought to be due to a combination of activa-tion of the Wnt⁄b-catenin pathway via inhibition of glycogen synthase kin-ase-3b and depletion of the inositol pool via inhibition of the inositol monophosphatase-1. | ỊFEBS Journal Lithium increases PGC-1a expression and mitochondrial biogenesis in primary bovine aortic endothelial cells Ian T. Struewing Corey D. Barnett Tao Tang and Catherine D. Mao Graduate Center for NutritionalSciences University of Kentucky Lexington USA Keywords cell signaling CREB FOXO gene expression mitochondria Correspondence C. D. Mao Graduate Center for Nutritional Sciences University of Kentucky 900 Limestone Street Lexington KY 40536 USA Fax 1 859 257 3646 Tel 1 859 323 4933 Ext. 81377 E-mail cdmao2@ Received 14 January 2007 revised 13 March 2007 accepted 23 March 2007 doi Lithium is a therapeutic agent commonly used to treat bipolar disorder and its beneficial effects are thought to be due to a combination of activation of the Wnt b-catenin pathway via inhibition of glycogen synthase kin-ase-3b and depletion of the inositol pool via inhibition of the inositol monophosphatase-1. We demonstrated that lithium in primary endothelial cells induced an increase in mitochondrial mass leading to an increase in ATP production without any significant change in mitochondrial efficiency. This increase in mitochondrial mass was associated with an increase in the mRNA levels of mitochondrial biogenesis transcription factors nuclear respiratory factor-1 and -2b as well as mitochondrial transcription factors A and B2 which lead to the coordinated upregulation of oxidative phosphorylation components encoded by either the nuclear or mitochondrial genome. These effects of lithium on mitochondrial biogenesis were independent of the inhibition of glycogen synthase kinase-3b and independent of inositol depletion. Also expression of the coactivator PGC-1a was increased whereas expression of the coactivator PRC was not affected. Lithium treatment rapidly induced a decrease in activating Akt-Ser473 phosphorylation and inhibitory Forkhead box class O FOXO1 -Thr24 phosphorylation as well as an increase in activating c-AMP responsive .