HtrA2 Interacts with Aβ Peptide but Does Not Directly Alter Its Production or Degradation

  • Liu, Meng-Lu (Department of Microbiology and Research Center for Industrial Development of Biofood Materials, Chonbuk National University Medical School) ;
  • Liu, Ming-Jie (Department of Microbiology and Research Center for Industrial Development of Biofood Materials, Chonbuk National University Medical School) ;
  • Kim, Jin-Man (Department of Microbiology and Research Center for Industrial Development of Biofood Materials, Chonbuk National University Medical School) ;
  • Kim, Hyeon-Jin (Jinis Biopharmaceuticals Company) ;
  • Kim, Jeong-Hak (Jinis Biopharmaceuticals Company) ;
  • Hong, Seong-Tshool (Department of Microbiology and Research Center for Industrial Development of Biofood Materials, Chonbuk National University Medical School)
  • Received : 2005.02.24
  • Accepted : 2005.04.06
  • Published : 2005.08.31

Abstract

HtrA2/Omi is a mammalian mitochondrial serine protease homologous to the E. coli HtrA/DegP gene products. Recently, HtrA2/Omi was found to have a dual role in mammalian cells, acting as an apoptosis-inducing protein and being involved in maintenance of mitochondrial homeostasis. By screening a human brain cDNA library with $A{\beta}$ peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of $A{\beta}$ peptide. The interaction between $A{\beta}$ peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in $A{\beta}$ peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of $A{\beta}$ peptide at the ${\beta}/{\gamma}$-secretase level, or the degradation of $A{\beta}$ peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of $A{\beta}40$ and $A{\beta}42$ by up to 30%. These results rule out the involvement of HtrA2/Omi in the etiology of Alzheimer's disease. However, the fact that overexpression of HtrA2/Omi reduces the generation of $A{\beta}40$ and $A{\beta}42$ suggests that it may play some positive role in mammalian cells.

Keywords

$A{\beta}$ Peptide;Alzheimer's Disease;Apoptosis;HtrA2/Omi;Mitochondria Homeostasis;Secretase

Acknowledgement

Supported by : Korean Ministry of Education

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