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Aging-related Correlation of Insulin-degrading Enzyme with γ-Secretase-generated Products Involving Insulin and Glucose Levels in Transgenic Mice

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Abstract

Insulin-degrading enzyme (IDE) is a 110-kDa thiol zinc-methalloendopeptidase that can cleave small Aβ peptides and the APP intracellular domain (AICD). The aim of this study was to examine aging-related correlation of IDE with γ-secretase-generated products involving insulin and glucose levels in transgenic brains expressing neuron-specific enolase (NSE)-controlled human mutant presenilin-2 (hPS2m). Herein, we concluded that the levels of IDE expression in transgenic brains were decreased relative to those of control mice at 15 months of age. In parallel, inhibition in the IDE expression at this age underlies to the levels-up of Aβ-42, AICD, γ-secretase, and glucose with a level-down of insulin. Thus, IDE expression is critical target for the therapeutic trials.

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References

  1. C. Glabe (2000) ArticleTitleDoes Alzheimer disease tilt the scales of amyloid degradation versus accumulation? Nat. med. 6 133–134 Occurrence Handle10.1038/72215 Occurrence Handle10655093 Occurrence Handle1:CAS:528:DC%2BD3cXosFyrtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  2. A. B. Becker R. A. Roth (1995) ArticleTitleInsulysin and pitrilysin: Insulin-degrading enzymes of mammals and bacteria Methods Enzymol. 248 693–703 Occurrence Handle7674956 Occurrence Handle1:CAS:528:DyaK2MXptVShsb0%3D

    PubMed  CAS  Google Scholar 

  3. D. Edbauer M. Willem S. Lammich H. Steiner C. Haass (2002) ArticleTitleInsulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD) J. Biol. Chem. 277 13389–13393 Occurrence Handle10.1074/jbc.M111571200 Occurrence Handle11809755 Occurrence Handle1:CAS:528:DC%2BD38XjsFWgtLc%3D

    Article  PubMed  CAS  Google Scholar 

  4. W. C. Duckworth R. G. Bennett F. G. Hamel (1998) ArticleTitleInsulin degradation: Progress and potential Endocr. Rev. 19 608–624 Occurrence Handle10.1210/er.19.5.608 Occurrence Handle9793760 Occurrence Handle1:CAS:528:DyaK1cXntV2rtb8%3D

    Article  PubMed  CAS  Google Scholar 

  5. I. D. Goldfine J. A. Williams A. C. Bailey K. Y. Wong Y. Iwamoto K. Yokono S. Baba R. A. Roth (1984) ArticleTitleDegradation of insulin by isolated mouse pancreatic acini. Evidence for cell surface protease activity Diabetes 33 64–72 Occurrence Handle6360769 Occurrence Handle1:CAS:528:DyaL2cXhtFGgsrg%3D

    PubMed  CAS  Google Scholar 

  6. K. A. Seta R. A. Roth (1997) ArticleTitleOverexpression of insulin-degrading enzyme: Cellular localization and effects on insulin signaling Biochem. Biophys. Res. Commun. 231 167–171 Occurrence Handle10.1006/bbrc.1997.6066 Occurrence Handle9070242 Occurrence Handle1:CAS:528:DyaK2sXht1als7g%3D

    Article  PubMed  CAS  Google Scholar 

  7. K. Vekrellis Z. Ye W. Q. Qiu D. Walsh V. Chesneau M. R. Rosner D. J. Selkoe (2000) ArticleTitleNeurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme J. Neurosci. 20 1657–1665 Occurrence Handle10684867 Occurrence Handle1:CAS:528:DC%2BD3cXhsVGmtr4%3D

    PubMed  CAS  Google Scholar 

  8. A. N. Sabirov Y. E. Kim H. J. Kim V. V. Samukov (1998) ArticleTitleFMOC- and NSC-groups as a base labile N(α)-amino protection: A comparative study in the automated SPPS Protein Peptide Lett. 5 57–62 Occurrence Handle1:CAS:528:DyaK1cXisFSgu7k%3D

    CAS  Google Scholar 

  9. N. Ida T. Hartmann J. Pantel J. Schroder R. Zerfass H. Forsti R. Sandbrink C. L. Masters K. Beyreuther (1996) ArticleTitleAnalysis of heterogeneous A4 peptide in human cerebrospinal fluid and blood by a newly developed sensitive western blot assay J. Biol. Chem. 271 22908–22914 Occurrence Handle8798471 Occurrence Handle1:CAS:528:DyaK28Xlslagu7g%3D

    PubMed  CAS  Google Scholar 

  10. D. Y. Hwang K. R. Chae T. S. Kang J. H. Hwang C. H. Lim H. K. Kang J. S. Goo M. R. Lee H. J. Lim S. H. Min J. Y. Cho J. T. Hong C. W. Song S. G. Paik J. S. Cho Y. K. Kim (2002) ArticleTitleAlterations in behavior, amyloid β-42, caspase-3, and Cox-2 in mutant PS2 transgenic mouse model of Alzheimer’s disease FASEB J. 16 805–813 Occurrence Handle10.1096/fj.01-0732com Occurrence Handle12039862 Occurrence Handle1:CAS:528:DC%2BD38XksVWmtL8%3D

    Article  PubMed  CAS  Google Scholar 

  11. W. Xia W. J. Ray B. L. Ostaszewski T. Rahmati W. T. Kimberly M. S. Wolfe J. Zhang A. M. Goate D. J. Selkoe (2000) ArticleTitlePresenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generation Proc. Natl. Acad. Sci. USA 97 9299–9304 Occurrence Handle10922078 Occurrence Handle1:CAS:528:DC%2BD3cXls12ktr0%3D

    PubMed  CAS  Google Scholar 

  12. J. Y. Cho D. Y. Hwang T. S. Kang D. H. Shin J. H. Hwang C. H. Lim S. H. Lee H. J. Lim S. H. Min S. J. Seo Y. S. Song K. T. Nam K. S. Lee J. S. Cho Y. K. Kim (2003) ArticleTitleUse of NSE/PS2m-transgenic mice in the study of the protective effect of exercise on Alzheimer’s disease J. Sports Sci. 21 943–951 Occurrence Handle10.1080/0264041031000140365 Occurrence Handle14626374

    Article  PubMed  Google Scholar 

  13. N. Iwata Y. Takaki S. Fukami S. Tsubuki T. C. Saido (2002) ArticleTitleRegion-specific reduction of Aβ-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging J.␣Neurosci. Res. 70 493–500 Occurrence Handle12391610 Occurrence Handle1:CAS:528:DC%2BD38XosVejsro%3D

    PubMed  CAS  Google Scholar 

  14. M. Mohajeri M. A. Wollmer R. M. Nitsch (2002) ArticleTitleAβ-42-induced increase in neprilysin is associated with prevention of amyloid plaque formation in vivo J. Biol. Chem. 277 35460–35465 Occurrence Handle12105192 Occurrence Handle1:CAS:528:DC%2BD38Xnt1Wmt7k%3D

    PubMed  CAS  Google Scholar 

  15. W. Farris S. Mansourian Y. Chang L. Lindsley E. A. Eckman M. P. Frosch C. B. Eckman R. E. Tanzi D. J. Selkoe S. Guenette (2003) ArticleTitleInsulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta- amyloid precursor protein intracellular domain in vivo Proc. Natl. Acad. Sci. USA 100 4162–4167 Occurrence Handle10.1073/pnas.0230450100 Occurrence Handle12634421 Occurrence Handle1:CAS:528:DC%2BD3sXivFWjsrk%3D

    Article  PubMed  CAS  Google Scholar 

  16. D. Scheuner C. Eckman M. Jensen X. Song M. Citron (1996) ArticleTitleSecreted amyloid β-protein similar to that in the senile plaques of Alzheimer’s disease Nat. Med. 2 864–870 Occurrence Handle10.1038/nm0896-864 Occurrence Handle8705854 Occurrence Handle1:CAS:528:DyaK28XkslGiu7g%3D

    Article  PubMed  CAS  Google Scholar 

  17. R. P. Stolk M. M. Breteler A. Ott H. A. Pols H. W. Lamberts D. E. Globbee A. Hofman (1997) ArticleTitleInsulin and cognitive function in an elderly population. The Rotterdam Study Diabetes Care. 20 792–795 Occurrence Handle9135944 Occurrence Handle1:STN:280:ByiB1c7mtlI%3D

    PubMed  CAS  Google Scholar 

  18. G. Razay G. K. Wilcock (1994) ArticleTitleHyperinsulinaemia and Alzheimer’s disease Age Ageing 23 396–399 Occurrence Handle7825486 Occurrence Handle1:STN:280:ByqC38ngtFw%3D

    PubMed  CAS  Google Scholar 

  19. Y. Fujisawa K. Sasaki K. Akiyama (1991) ArticleTitleIncreased insulin levels after OGTT load in peripheral blood and cerebrospinal fluid of patients with dementia of Alzheimer type Biol. Psychia. 30 1219–1228 Occurrence Handle1:STN:280:By2C283ovFM%3D

    CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Laboratory Animal Resources, , National Institute of Toxicological Research, Korea FDA, Seoul, 122-704, Korea

    Dae Y. Hwang, Jung S. Cho, Chuel K. Kim, Sun B. Shim, Seung W. Jee, Su H. Lee, Su J. Seo & Yong K. Kim

  2. Exercise Biochemistry Laboratory, Korea National Sport University, 138-763, Korea

    Joon Y. Cho

  3. National Institute of Toxicological Research, Korea FDA, 122-704, Seoul, Korea

    Seok H. Lee

Authors
  1. Dae Y. Hwang
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  2. Jung S. Cho
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  3. Chuel K. Kim
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  4. Sun B. Shim
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  5. Seung W. Jee
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  6. Su H. Lee
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  7. Su J. Seo
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  8. Joon Y. Cho
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  9. Seok H. Lee
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  10. Yong K. Kim
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Correspondence to Chuel K. Kim.

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Hwang, D.Y., Cho, J.S., Kim, C.K. et al. Aging-related Correlation of Insulin-degrading Enzyme with γ-Secretase-generated Products Involving Insulin and Glucose Levels in Transgenic Mice. Neurochem Res 30, 1171–1177 (2005). https://doi.org/10.1007/s11064-005-7952-7

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  • DOI: https://doi.org/10.1007/s11064-005-7952-7

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