TY - JOUR
T1 - Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression
AU - Chandrasekaran, Krish
AU - Liu, Li Ing
AU - Hatanpää, Kimmo
AU - Shetty, Umesha
AU - Mehrabian, Zara
AU - Murray, Peter D.
AU - Fiskum, Gary
AU - Rapoport, Stanley I.
N1 - Funding Information:
This work was supported by the grants from the US Army DAMD17-99-1-9483 to G.F., from NIH AG16966A to K.C., and from AHA 0051001U to K.C.
PY - 2001/8
Y1 - 2001/8
N2 - 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 β-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 β-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.
AB - 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 β-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 β-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.
KW - Intracellular sodium
KW - Mitochondrial mRNA
KW - Neural cells
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U2 - 10.1016/S1567-7249(01)00010-1
DO - 10.1016/S1567-7249(01)00010-1
M3 - Article
C2 - 16120274
AN - SCOPUS:0039782245
SN - 1567-7249
VL - 1
SP - 141
EP - 150
JO - Mitochondrion
JF - Mitochondrion
IS - 2
ER -