Involvement of Interleukin-1 in Lead Nitrate-Induced Hypercholesterolemia in Mice
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- Kojima Misaki
- Animal Genome Research Unit, Agrogenomics Research Center, National Institute of Agrobiological Sciences
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- Ashino Takashi
- Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University
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- Yoshida Takemi
- Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University
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- Iwakura Yoichiro
- Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
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- Degawa Masakuni
- Department of Molecular Toxicology and Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka
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Abstract
Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and cholesterol 7α-hydroxylase (Cyp7a1) are rate-limiting enzymes for cholesterol biosynthesis and catabolism, respectively. Involvement of inflammatory cytokines, particularly interleukin-1 (IL-1), in alterations of HMGR and Cyp7a1 gene expression during development of lead nitrate (LN)-induced hypercholesterolemia was examined in IL-1α/β-knockout (IL-1-KO) and wild-type (WT) mice. Lead nitrate treatment of WT mice led to not only a marked downregulation of the Cyp7a1 gene at 6—12 h, but also a significant upregulation of the HMGR gene at 12 h. However, such changes were not observed at significant levels in IL-1-KO mice, although a slight, transient downregulation of the Cyp7a1 gene and a minimal upregulation of the HMGR gene occurred at 6 h and 24 h, respectively. Consequently, LN treatment led to development of hypercholesterolemia at 24 h in WT mice, but not in IL-1-KO mice. Furthermore, in WT mice, significant LN-mediated increases were observed at 3—6 h in hepatic IL-1 levels, which can modulate gene expression of Cyp7a1 and HMGR. These findings indicate that, in mice, LN-mediated increases in hepatic IL-1 levels contribute, at least in part, to altered expressions of Cyp7a1 and HMGR genes, and eventually to hypercholesterolemia development.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 35 (2), 246-250, 2012
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390001204631865728
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- NII Article ID
- 130001872300
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- NII Book ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC387pt1ylsg%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 023409576
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- PubMed
- 22293356
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed