徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.疾患酵素学研究センター(2007年4月1日〜2016年3月31日/->組織[徳島大学.先端酵素学研究所.次世代酵素学研究領域])

1. Yao Min

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2. Yao Dengbing

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3. (英) Yamaguchi Miyoko

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4. 千田 淳司([徳島大学.先端酵素学研究所.基幹研究部門])

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5. (英) Yao Dengfu

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6. 木戸 博([徳島大学.先端酵素学研究所.重点研究部門])

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(英) Bezafibrate upregulates carnitine palmitoyltransferase II expression and promotes mitochondrial energy crisis dissipation in fibroblasts of patients with influenza-associated encephalopathy

(英) Influenza-associated encephalopathy (IAE) is characterized by persistently high fever, febrile convulsions, severe brain edema and high mortality. We reported previously that a large proportion of patients with disabling or fatal IAE exhibit a thermolabile phenotype of compound variants for [1055T>G/F352C] and [1102G>A/V368I] of carnitine palmitoyltransferase II (CPT II) and mitochondrial energy crisis during high fever. In the present study, we studied the effect of bezafibrate, a hypolipidemic pan-agonist of peroxisome proliferator-activated receptor (PPAR), on CPT II expression and mitochondrial energy metabolism in fibroblasts of IAE patients and wild type (WT) fibroblasts from a healthy volunteer at 37°C and 41°C. Although heat stress markedly upregulated CPT II, CPT IA and PPAR-δ mRNA expression levels, CPT II activity, β-oxidation and ATP levels in WT and IAE fibroblasts at 41°C were paradoxically downregulated probably due to the thermal instability of the corresponding enzymes. Bezafibrate significantly enhanced the expression levels of the above mRNAs and cellular functions of these enzymes in fibroblasts at 37°C. Bezafibrate-induced increase in CPT II activity also tended to restore the downregulated ATP levels, though moderately, and improved mitochondrial membrane potential even at 41°C to the levels at 37°C in fibroblasts of IAE patients. L-carnitine, a substrate of CPT II, boosted the effects of bezafibrate on cellular ATP levels in WT and IAE fibroblasts, even in severe IAE fibroblasts with thermolabile compound variations of F352C+V368I at 37°C and 41°C. The results suggest the potential usefulness of bezafibrate for the treatment of IAE.

1. (英) Adenosine Triphosphate
2. (英) Base Sequence
3. (英) Bezafibrate
4. (英) Blotting, Western
5. (英) Brain Diseases, Metabolic
6. (英) Carnitine
7. (英) Carnitine O-Palmitoyltransferase
8. (英) DNA Primers
9. (英) Energy Metabolism
10. (英) Fibroblasts
11. (英) Gene Expression Regulation
12. (英) Genomics
13. (英) Hot Temperature
14. (英) Humans
15. (英) Influenza, Human
16. (英) Japan
17. (英) Membrane Potential, Mitochondrial
18. (英) Microscopy, Fluorescence
19. (英) Mitochondria
20. (英) Molecular Sequence Data
21. (英) Peroxisome Proliferator-Activated Receptors
22. (英) RNA, Messenger
23. (英) Real-Time Polymerase Chain Reaction
24. (英) Sequence Analysis, DNA
25. (英) Time Factors

1. (英) Article.Affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Comparative Study

3. (英) Article.PublicationTypeList.PublicationType: Journal Article

4. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't