Skip to main content
SpringerLink
Log in

Sterol Regulatory Element-Binding Protein-2 modulates human brain acyl-CoA hydrolase gene transcription

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The brain shows high catalyzing activity during hydrolysis of long-chain acyl-CoAs into fatty acids and CoA-SH. Brain acyl-CoA hydrolase (BACH) is responsible for most of the long-chain acyl-CoA hydrolyzing activity in the brain and is localized exclusively in neurons. We analyzed the human BACH gene promoter, focusing on transcriptional regulation by Sterol Regulatory Element-Binding Protein-2 (SREBP-2), which is a transcription factor that activates genes involved in cholesterol biosynthesis and uptake. When the nuclear form of SREBP-2 gene was transfected into human neuroblastoma cells, transcription of a BACH gene promoter-luciferase reporter gene was activated through a sterol regulatory element (SRE) motif. Moreover, a gel shift assay demonstrated that SREBP-2 specifically bound to the SRE motif. These results suggest that transcription of the BACH gene is activated by SREBP-2. This study also provides insights into BACH function in the interaction between the metabolism of acyl-CoAs and cholesterol in neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Faergeman NJ, Knudsen J: Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem J. 323: 1–12, 1997

    Google Scholar 

  2. Waku K: Origins and fates of fatty acyl-CoA esters. Biochim Biophys Acta 1124: 101–111, 1992

    Google Scholar 

  3. Hunt MC, Alexson SE: The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism. Prog Lipid Res 41: 99–130, 2002

    Google Scholar 

  4. Anderson AD, Erwin VG: Brain acyl-coenzyme A hydrolase: Distribution, purification and properties. J Neurochem 18: 1179–1186, 1971

    Google Scholar 

  5. Katoh H, Kawashima Y, Watanuki H, Kozuka H, Isono H: Effects of clofibric acid and tiadenol on cytosolic long-chain acyl-CoA hydrolase and peroxisomal beta-oxidation in liver and extrahepatic tissues of rats. Biochim Biophys Acta 920: 171–179, 1987

    Google Scholar 

  6. Knauer TE: Factors affecting the activity and stability of the palmitoyl-coenzyme A hydrolase of rat brain. Biochem J. 179: 515–523, 1979

    Google Scholar 

  7. Lin AY, Sun GY, MacQuarrie R: Partial purification and properties of long-chain acyl-CoA hydrolase from rat brain cytosol. Neurochem Res. 9: 1571–1591, 1984

    Google Scholar 

  8. Broustas CG, Hajra AK: Purification, properties, and specificity of rat brain cytosolic fatty acyl coenzyme A hydrolase. J. Neurochem 64: 2345–2353, 1995

    Google Scholar 

  9. Kuramochi Y, Takagi-Sakuma M, Kitahara M, Emori R, Asaba Y, Sakaguchi R, Watanabe T, Kuroda J, Hiratsuka K, Nagae Y, Suga T, Yamada J: Characterization of mouse homolog of brain acyl-CoA hydrolase: Molecular cloning and neuronal localization. Brain Res Mol Brain Res 98: 81–92, 2002

    Google Scholar 

  10. Yamada J, Furihata T, Iida N, Watanabe T, Hosokawa M, Satoh T, Someya A, Nagaoka I, Suga T: Molecular cloning and expression of cDNAs encoding rat brain and liver cytosolic long-chain acyl-CoA hydrolases. Biochem Biophys Res Commun 232: 198–203, 1997

    Google Scholar 

  11. Yamada J, Kuramochi Y, Takagi M, Suga T: Expression of acyl-CoA hydrolase in the developing mouse brain. Neurosci Lett 355: 89–92, 2004

    Google Scholar 

  12. Yamada J, Kurata A, Hirata M, Taniguchi T, Takama H, Furihata T, Shiratori K, Iida N, Takagi-Sakuma M, Watanabe T, Kurosaki K, Endo T, Suga T: Purification, molecular cloning, and genomic organization of human brain long-chain acyl-CoA hydrolase. J Biochem (Tokyo) 126: 1013–1019, 1999

    Google Scholar 

  13. Yamada J, Kuramochi Y, Takagi M, Watanabe T, Suga T: Human brain acyl-CoA hydrolase isoforms encoded by a single gene. Biochem Biophys Res Commun 299: 49–56, 2002

    Google Scholar 

  14. Takagi M, Kawabe K, Suga T, Yamada J: A 50-kDa isoform of mouse brain acyl-CoA hydrolase: expression and molecular properties. Arch Biochem Biophys 429: 100–105, 2004

    Google Scholar 

  15. Brown MS, Goldstein JL: The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89: 331–340, 1997

    Google Scholar 

  16. Krieger M: Isolation of somatic cell mutants with defects in the endocytosis of low-density lipoprotein. Methods Enzymol 129: 227–237, 1986

    Google Scholar 

  17. Maruyama K, Sugano S: Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 138: 171–174, 1994

    Google Scholar 

  18. Lo K, Smale ST: Generality of a functional initiator consensus sequence. Gene 182: 13–22, 1996

    Google Scholar 

  19. Athanikar JN, Sanchez HB, Osborne TF: Promoter selective transcriptional synergy mediated by sterol regulatory element binding protein and Sp1: A critical role for the Btd domain of Sp1. Mol Cell Biol 17: 5193–5200, 1997

    Google Scholar 

  20. Sato R, Inoue J, Kawabe Y, Kodama T, Takano T, Maeda M: Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2. J Biol Chem 271: 26461–26464, 1996

    Google Scholar 

  21. Yamada J, Furihata T, Tamura H, Watanabe T, Suga T: Long-chain acyl-CoA hydrolase from rat brain cytosol: Purification, characterization, and immunohistochemical localization. Arch Biochem Biophys 326: 106–114, 1996

    Google Scholar 

  22. Sato R, Miyamoto W, Inoue J, Terada T, Imanaka T, Maeda M: Sterol regulatory element-binding protein negatively regulates microsomal triglyceride transfer protein gene transcription. J Biol Chem 274: 24714–24720, 1999

    Google Scholar 

  23. del Castillo-Olivares A, Gil G: Differential effects of sterol regulatory binding proteins 1 and 2 on sterol 12 alpha-hydroxylase. SREBP-2 suppresses the sterol 12 alpha-hydroxylase promoter. J Biol Chem 277: 6750–6757, 2002

    Google Scholar 

  24. Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS: Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest 99: 838–845, 1997

    Google Scholar 

  25. Hunt MC, Solaas K, Kase BF, Alexson SE: Characterization of an Acyl-CoA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. J Biol Chem 277: 1128–1138, 2002

    Google Scholar 

  26. Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J: Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18: 551–561, 1987

    Google Scholar 

  27. Takagi M, Yamakawa H, Watanabe T, Suga T, Junji Y: Inducible expression of long-chain acyl-CoA hydrolase gene in cell cultures. Mol Cell Biochem 252: 379–385, 2003

    Google Scholar 

  28. Thompson AL, Cooney GJ: Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 49: 1761–1765, 2000

    Google Scholar 

  29. Boylan JG, Hamilton JA: Interactions of acyl-coenzyme A with phosphatidylcholine bilayers and serum albumin. Biochemistry 31: 557–567, 1992

    Google Scholar 

  30. Yanase H, Shimizu H, Yamada K, Iwanaga T: Cellular localization of the diazepam binding inhibitor in glial cells with special reference to its coexistence with brain-type fatty acid binding protein. Arch Histol Cytol 65: 27–36, 2002

    Google Scholar 

  31. Pfrieger FW: Outsourcing in the brain: Do neurons depend on cholesterol delivery by astrocytes? Bioessays 25: 72–78, 2003

    Google Scholar 

  32. Maloberti P, Mele PG, Neuman I, Cornejo Maciel F, Cano F, Bey P, Paz C, Podesta EJ: Regulation of arachidonic acid release in steroidogenesis: Role of a new acyl-CoA thioestrase (ARTISt). Endocr Res 26: 653–662, 2000

    Google Scholar 

  33. Puglielli L, Konopka G, Pack-Chung E, Ingano LA, Berezovska O, Hyman BT, Chang TY, Tanzi RE, Kovacs DM: Acyl-coenzyme A: Cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat Cell Biol 3: 905–912, 2001

    Google Scholar 

  34. Selkoe DJ: Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature 399: A23–A31, 1999

    Google Scholar 

  35. Tanzi RE: A genetic dichotomy model for the inheritance of Alzheimer’s disease and common age-related disorders. J Clin Invest 104: 1175–1179, 1999

    Google Scholar 

  36. Chang TY, Chang CC, Cheng D: Acyl-coenzyme A: Cholesterol acyltransferase. Annu Rev Biochem 66: 613–638, 1997

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science, Tokyo, Japan

    Mitsuhiro Takagi, Fumitaka Suto, Tetsuya Suga & Junji Yamada

  2. Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Mitsuhiro Takagi

Authors
  1. Mitsuhiro Takagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumitaka Suto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tetsuya Suga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junji Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitsuhiro Takagi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takagi, M., Suto, F., Suga, T. et al. Sterol Regulatory Element-Binding Protein-2 modulates human brain acyl-CoA hydrolase gene transcription. Mol Cell Biochem 275, 199–206 (2005). https://doi.org/10.1007/s11010-005-1990-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-1990-y

Keywords

Search

Navigation