title: Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression.
abstract: Regulation of expression of mitochondrial DNA- (mtDNA-) encoded genes of oxidative phosphorylation can occur rapidly in neural cells subjected to a variety of physiological and pathological conditions. However, the intracellular signal(s) involved in regulating these processes remain unknown. Using mtDNA-encoded cytochrome oxidase subunit III (COX III), we show that its mRNA expression in a differentiated rat pheochromocytoma cell line PC12S is decreased by chronic exposure to agents that increase intracellular sodium. Treatment of differentiated PC12S cells either with ouabain, an inhibitor of Na/K-ATPase, or with monensin, a sodium ionophore, decreased the steady-state levels of COX III mRNA by 50%, 3-4 h after addition of the drugs. No significant reduction in mtDNA-encoded 12S rRNA or nuclear DNA-encoded beta-actin mRNA were observed. Removal of the drugs restored the normal levels of COX III mRNA. Determination of half-lives of COX III mRNA, 12S rRNA, and beta-actin mRNA revealed a selective decrease in the half-life of COX III mRNA from 3.3 h in control cells to 1.6 h in ouabain-treated cells, and to 1 h in monensin-treated cells. These results suggest the existence of a mechanism of posttranscriptional regulation of mitochondrial gene expression that is independent of the energetic status of the cell and may operate under pathological conditions.
authors.affiliation: Department of Anesthesiology, University of Maryland School of Medicine, MSTF 5-34, 685 West Baltimore Street, Baltimore, MD 21201, USA. kchandra@anesthlab.ummc.umaryland.edu
authors.forename: K
authors.initials: K
authors.lastname: Chandrasekaran
authors.forename: L I
authors.initials: LI
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Hatanpää
authors.forename: U
authors.initials: U
authors.lastname: Shetty
authors.forename: Z
authors.initials: Z
authors.lastname: Mehrabian
authors.forename: P D
authors.initials: PD
authors.lastname: Murray
authors.forename: G
authors.initials: G
authors.lastname: Fiskum
authors.forename: S I
authors.initials: SI
authors.lastname: Rapoport