| Autor: |
Gayathri Ramaswamy, Mohammad A. Karim, K. Gopal Murti, Suzanne Jackowski |
| Jazyk: |
angličtina |
| Rok vydání: |
2004 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 45, Iss 1, Pp 17-31 (2004) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M300279-JLR200 |
| Popis: |
Pantothenate kinase (PanK) is thought to catalyze the first rate-limiting step in CoA biosynthesis. The full-length cDNA encoding the human PanK1α protein was isolated, and the complete human PANK1 gene structure was determined. Bezafibrate (BF), a hypolipidemic drug and a peroxisome proliferator activator receptor-α (PPARα) agonist, specifically increased hPANK1α mRNA expression in human hepatoblastoma (HepG2) cells as a function of time and dose of the drug, compared with hPANK1β, hPANK2, and hPANK3, which did not significantly increase. Four putative PPARα response elements were identified in the PANKIα promoter, and BF stimulated hPANK1α promoter activity but did not alter the mRNA half-life. Increased hPANK1α mRNA resulted in higher hPanK1 protein, localized in the cytoplasm, and elevated PanK enzyme activity. The enhanced hPANK1α 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 PanK1α in the control of cellular CoA content and point to the PPARα transcription factor as a major factor governing hepatic CoA levels by specific modulation of PANK1α gene expression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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