TY - JOUR
T1 - FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes
AU - Kagawa, Yoshiteru
AU - Umaru, Banlanjo Abdulaziz
AU - Shima, Hiroki
AU - Ito, Ryo
AU - Zama, Ryo
AU - Islam, Ariful
AU - Kanno, Shin ichiro
AU - Yasui, Akira
AU - Sato, Shun
AU - Jozaki, Kosuke
AU - Shil, Subrata Kumar
AU - Miyazaki, Hirofumi
AU - Kobayashi, Shuhei
AU - Yamamoto, Yui
AU - Kogo, Hiroshi
AU - Shimamoto-Mitsuyama, Chie
AU - Sugawara, Akira
AU - Sugino, Norihiro
AU - Kanamori, Masayuki
AU - Tominaga, Teiji
AU - Yoshikawa, Takeo
AU - Fukunaga, Kohji
AU - Igarashi, Kazuhiko
AU - Owada, Yuji
N1 - Funding Information:
We thank Dr. Toyoshi Fujimoto for the reporter constructs of caveolin-1 promoter and for comments on this work. We thank Dr. Majid Ebrahimi, Mr. Kazutake Yagi, Mr. Toshiaki Abe, and Ms. Yoko Katsumata for technical support and the Biomedical Research Unit of Tohoku University Hospital for their support. All data generated or analyzed during this study are included in this published article and its supplementary information files.
Funding Information:
This work was supported in part by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 15K16206, No. 17K15539 and 20K11527 to Y.K., No. 16H05116, and No. 19H04026 to Y. O.), in part by AMED under Grant Number JP17dm0107071 (to K.F. and Y.O.), and in part by the GSK Japan Research Grant 2015 (to Y.K.). Acknowledgments Availability of Data and Material Code Availability
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.
AB - Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.
KW - ATP-citrate lyase (ACLY)
KW - Acetyl-CoA
KW - Astrocyte
KW - Caveolin-1
KW - Fatty acid–binding protein (FABP)
KW - Histone acetylation
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U2 - 10.1007/s12035-020-02057-3
DO - 10.1007/s12035-020-02057-3
M3 - Article
C2 - 32812201
AN - SCOPUS:85089503754
VL - 57
SP - 4891
EP - 4910
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
IS - 12
ER -