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Prolyl Endopeptidase Cleaves the Apoptosis Rescue Peptide Humanin and Exhibits an Unknown Post-Cysteine Cleavage Specificity

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Dipeptidyl Aminopeptidases

4. Conclusion

The data presented, demonstrate for the first time PEP turnover of HN by a limited postcysteine as well as the expected post-proline proteolysis demonstrated in cell extract resulting in the inactivation of this potentially apoptosis-related factor. These findings lead to the hypothesis of a PEP-mediated control of HN homeostasis maintaining neuronal cell survival. This implicates a novel use of PEP inhibitors potentially preventing intracellular HN digestion. Consequently, PEP-inhibition might be a new target for apoptosis prevention.

This study further uncovered a so far unknown enzymatic specificity for a post-cysteine cleavage of the mammalian exopeptidases DP2, DP4, DP8 and DP9 and the endopeptidase PEP.

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References

  • Bär J, Weber A, Hoffmann T, Stork J, Wermann M, Wagner L, Aust S, Gerhartz B and Demuth HU, 2003, Characterisation of human dipeptidyl peptidase IV expressed in Pichia pastoris. A structural and mechanistic comparison between the recombinant human and the purified porcine enzyme. Biol Chem. 384: 1553–1563.

    Article  PubMed  Google Scholar 

  • Dresdner K, Barker LA, Orlowski M, and Wilk S, 1982, Subcellular distribution of prolyl endopeptidase and cation-sensitive neutral endopeptidase in rabbit brain. J Neurochem. 38: 1151–1154.

    Article  CAS  PubMed  Google Scholar 

  • Goossens F, De Meester I, Vanhoof G and Scharpe S, 1996, Distribution of prolyl oligopeptidase in human peripheral tissues and body fluids. Eur J Clin Chem Clin Biochem. 34: 17–22.

    CAS  PubMed  Google Scholar 

  • Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC and Reed JC, 2003, Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 423: 456–461.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K and Nishimoto I, 2001, A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Abeta. Proc Natl Acad Sci USA. 98: 6336–6341.

    Article  CAS  PubMed  Google Scholar 

  • Irazusta J, Gil J, Ruiz F, Agirregoitia N, Casis L and Silveira PF, 2002, Effect of the disruption of body fluid balance on pyroglutamyl aminopeptidase (Type-1) in rat brain structures. Neuropeptides. 36: 333–340.

    Article  CAS  PubMed  Google Scholar 

  • Kariya S, Takahashi N, Hirano M and Ueno S, 2003, Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes. Mol Cell Biochem. 254: 83–89.

    Article  CAS  PubMed  Google Scholar 

  • Katsube N, Sunaga K, Aishita H, Chuang DM and Ishitani R, 1999, ONO-1603, a potential antidementia drug, delays age-induced apoptosis and suppresses overexpression of glyceraldehyde-3-phosphate dehydrogenase in cultured central nervous system neurons. J Pharmacol Exp Ther. 288: 6–13.

    CAS  PubMed  Google Scholar 

  • Mentlein R, 1988, Proline residues in the maturation and degradation of peptide hormones and neuropeptides. FEBS Lett. 234: 251–256.

    Article  CAS  PubMed  Google Scholar 

  • Polgar L, 1994, Prolyl oligopeptidases. Methods Enzymol. 244: 188–200.

    Article  CAS  PubMed  Google Scholar 

  • Schulz I, Gerhartz B, Neubauer A, Holloschi A, Heiser U, Hafner M and Demuth HU, 2002, Modulation of inositol 1,4,5-triphosphate concentration by prolyl endopeptidase inhibition. Eur J Biochem. 269: 5813–5820.

    Article  CAS  PubMed  Google Scholar 

  • Shishido Y, Furushiro M, Tanabe S, Shibata S, Hashimoto S and Yokokura T, 1999, Effects of prolyl endopeptidase inhibitors and neuropeptides on delayed neuronal death in rats. Eur J Pharmacol. 372: 135–142.

    Article  CAS  PubMed  Google Scholar 

  • Sponne I, Fifre A, Koziel V, Kriem B, Oster T and Pillot T, 2004, Humanin rescues cortical neurons from prionpeptide-induced apoptosis. Mol Cell Neurosci. 25: 95–102.

    Article  CAS  PubMed  Google Scholar 

  • Welches WR, Brosnihan KB and Ferrario CM, 1993, Acomparison of the properties and enzymatic activities of three angiotensin processing enzymes: angiotensin converting enzyme, prolyl endopeptidase and neutral endopeptidase 24.11. Life Sci. 52: 1461–1480.

    Article  CAS  PubMed  Google Scholar 

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Bär, J.W. et al. (2006). Prolyl Endopeptidase Cleaves the Apoptosis Rescue Peptide Humanin and Exhibits an Unknown Post-Cysteine Cleavage Specificity. In: Lendeckel, U., Reinhold, D., Bank, U. (eds) Dipeptidyl Aminopeptidases. Advances in Experimental Medicine and Biology, vol 575. Springer, Boston, MA . https://doi.org/10.1007/0-387-32824-6_11

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