Dexamethasone treatment increases mitochondrial RNA synthesis in a rat hepatoma cell line.
Glucocorticoid hormones act in the nucleus of the cell to alter expression of specific genes and change cell metabolism. In liver, these hormones have been reported to increase mitochondrial respiratory activity, which is regulated by both nuclear and mitochondrial gene products. We examined the effects of the synthetic glucocorticoid, dexamethasone, on the expression of mitochondrially encoded genes in a rat hepatoma cell line, H-4-II-E cells. Dexamethasone treatment of these cells increased mitochondrial RNA (mtRNA) levels 3- to 4-fold without changing the amount of mitochondrial DNA mtRNA levels could increase by enhanced mitochondrial gene transcription, by decreased degradation, or by some combination of the two. To determine if messenger RNA (mRNA) stabilization contributed to the increase in mtRNA levels, we compared the decay rates of cytochrome b mRNA from dexamethasone-treated and control cells after inhibition of RNA synthesis; cytochrome b mRNA half-life was 80 min in both treatment conditions. The levels of incompletely processed RNA precursors for at least two mtRNAs increased 3-fold more and 24 h earlier than the mature mRNAs. These results suggested that dexamethasone treatment resulted in increased mtRNA transcription. In addition, we examined the incorporation of [3H]uridine into mtRNA. Dexamethasone treatment expanded the uridine triphosphate pools 1.6-fold in H-4-II-E cells and decreased uridine triphosphate specific activity 2.3-fold; correcting for this change in precursor pool specific activity demonstrated increased mtRNA synthesis in dexamethasone-treated cells. Changes in expression of nuclear-encoded proteins that regulate mitochondrial genome transcription are a possible mechanism by which dexamethasone can increase mtRNA levels in these cells.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
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Van Itallie
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D003573:Cytochrome b Group / Q000096:biosynthesis / Q000235:genetics; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D046911:Macromolecular Substances; D012313:RNA / Q000096:biosynthesis* / Q000302:isolation & purification; D012322:RNA Precursors / Q000378:metabolism; D000077278:RNA, Mitochondrial; D051381:Rats; D014316:Tritium; D014529:Uridine / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D046911:Macromolecular Substances; D012322:RNA Precursors; D000077278:RNA, Mitochondrial; D014316:Tritium; D012313:RNA; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D014544:Uridine Triphosphate; D014529:Uridine