Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ahvaz Jundishapur University of Medical Sciences

Mechanism for FGF-1 to regulate biogenesis of apoE-HDL in astrocytes

Ito, J. I. and Nagayasu, Y. and Okumura-Noji, K. and Lu, R. and Nishida, T. and Miura, Y. and Asai, K. and Kheirollah, A. and Nakaya, S. and Yokoyama, S. (2007) Mechanism for FGF-1 to regulate biogenesis of apoE-HDL in astrocytes. Journal of Lipid Research, 48 (9). pp. 2020-2027. ISSN 00222275 (ISSN)

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Fibroblast growth factor-1 (FGF-1) is secreted by astrocytes and stimulates apolipoprotein E (apoE)-HDL biogenesis by an autocrine mechanism to help in recovery from brain injury. In apoE-deficient mouse astrocytes, FGF-1 stimulated cholesterol biosynthesis without enhancing its release, indicating a signaling pathway independent of apoE biosynthesis upregulation. SU5402, an inhibitor of FGF receptor, inhibited FGF-1-induced phosphorylation of MEK, ERK, and Akt, as well as all the apoE-HDL biogenesis-related events in rat astrocytes. LY294002, an inhibitor of phosphatidylinositide 3-OH kinase (PI3K) and of Akt phosphorylation, inhibited apoE-HDL secretion but not cholesterol biosynthesis, whereas U0126, an inhibitor of MEK and of ERK phosphorylation, inhibited cholesterol biosynthesis but not apoE-HDL secretion. Increase of apoE-mRNA by FGF-1 was not influenced by either inhibitor. When rat apoE/pcDNA3. his was transfected to transformed rat astrocyte GA-1 cells that otherwise do not synthesize apoE (GA-1/25), FGF-1 did not influence apoE-mRNA, but did increase the apoE secretion and Akt phosphorylation that were suppressed by LY294002. Lipid biosynthesis was increased by FGF-1 in GA-1/25 cells and suppressed by U0126. FGF-1 upregulates apoE-HDL biogenesis by three independent signaling pathways. The PI3K/Akt pathway upregulates secretion of apoE/apoE-HDL, the MEK/ERK pathway stimulates cholesterol biosynthesis, and an unknown pathway enhances apoE transcription. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc.

Item Type: Article
Keywords: Akt Apolipoprotein E-high density lipoprotein Astrocytes ERK MEK PI3K 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene 2 morpholino 8 phenylchromone 3 4 methyl 2 (2 oxo 3 indolinylmethylidenyl) 3 pyrrolylpropionic acid apolipoprotein E DNA fibroblast growth factor 1 high density lipoprotein messenger RNA mitogen activated protein kinase phosphatidylinositol 3 kinase protein kinase B animal cell article astrocyte biogenesis biosynthesis cholesterol synthesis controlled study DNA transfection enzyme phosphorylation fetus genetic transcription nonhuman priority journal protein secretion rat signal transduction upregulation Animals Apolipoproteins E Butadienes Chromones Lipids Lipoproteins, HDL MAP Kinase Kinase Kinases Mice Mice, Inbred C57BL Morpholines Nitriles Pyrroles Rats Rats, Wistar Receptors, Fibroblast Growth Factor
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences
Depositing User: مهندس مهدی شریفی
Last Modified: 01 Jun 2018 13:14

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