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PPARalpha controls the intracellular coenzyme A concentration via regulation of PANK1alpha gene expression.
- Source :
-
Journal of lipid research [J Lipid Res] 2004 Jan; Vol. 45 (1), pp. 17-31. Date of Electronic Publication: 2003 Oct 01. - Publication Year :
- 2004
-
Abstract
- Pantothenate kinase (PanK) is thought to catalyze the first rate-limiting step in CoA biosynthesis. The full-length cDNA encoding the human PanK1alpha protein was isolated, and the complete human PANK1 gene structure was determined. Bezafibrate (BF), a hypolipidemic drug and a peroxisome proliferator activator receptor-alpha (PPARalpha) agonist, specifically increased hPANK1alpha mRNA expression in human hepatoblastoma (HepG2) cells as a function of time and dose of the drug, compared with hPANK1beta, hPANK2, and hPANK3, which did not significantly increase. Four putative PPARalpha response elements were identified in the PANKIalpha promoter, and BF stimulated hPANK1alpha promoter activity but did not alter the mRNA half-life. Increased hPANK1alpha mRNA resulted in higher hPanK1 protein, localized in the cytoplasm, and elevated PanK enzyme activity. The enhanced hPANK1alpha gene expression translated into increased activity of the CoA biosynthetic pathway and established a higher steady-state CoA level in HepG2 cells. These data are consistent with a key role for PanK1alpha in the control of cellular CoA content and point to the PPARalpha transcription factor as a major factor governing hepatic CoA levels by specific modulation of PANK1alpha gene expression.
- Subjects :
- Amino Acid Sequence
Animals
Bezafibrate pharmacology
Cell Line
DNA, Complementary genetics
Exons genetics
Half-Life
Haplorhini
Humans
Introns genetics
Molecular Sequence Data
Organ Specificity
Phosphorylation
Promoter Regions, Genetic genetics
RNA Stability
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, Cytoplasmic and Nuclear agonists
Sequence Alignment
Sulfhydryl Compounds metabolism
Transcription Factors agonists
Coenzyme A metabolism
Gene Expression Regulation
Phosphotransferases (Alcohol Group Acceptor) genetics
Phosphotransferases (Alcohol Group Acceptor) metabolism
Receptors, Cytoplasmic and Nuclear metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2275
- Volume :
- 45
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 14523052
- Full Text :
- https://doi.org/10.1194/jlr.M300279-JLR200