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31.
Natalia N. Nalivaeva Lilia Fisk Rosa M. Canet. Aviles Svetlana A. Plesneva Igor A. Zhuravin Anthony J. Turner 《International journal of peptide research and therapeutics》2003,10(5-6):455-462
Summary In the present study we have investigated the effect of prenatal hypoxia on expression of amyloid precursor protein (APP)
and some metallopeptidases, which regulate β-amyloid peptide (Aβ) levels (neprilysin (NEP) and endothelin-converting enzyme
(ECE-1)) in the cortex of rats during different periods of postnatal development. We have found that the level of APP in the
sensorimotor cortex (SMC) of rats, analysed by Western blotting, increases from days 1 to 5 of postnatal development and then
steadily decreases with age, with the most dramatic decline in the period from day 180 to 600. In the cortex of rats subjected
to prenatal hypoxia on day 13.5 of embryogenesis, the postnatal levels of APP were higher than in the control. Secretion of
the soluble form of APP (sAPP) by α-secretase was found to be the most active on day 30 of postnatal development and there
was a significant decrease in the production of sAPP after prenatal hypoxia. NEP was found to be expressed in the cortex of
rats only at the early stages of postnatal development and it was barely detectable in adult rats. The decline of NEP levels
during ageing might contribute to accumulation of Aβ in later life in humans. Prenatal hypoxia resulted in a significant decrease
of NEP expression on day 10, but its level was recovered when animals were preconditioned to mild hypoxia. A similar phenomenon
was observed when the expression of ECE-1 was analysed. Overall, prenatal hypoxia leads to significant changes in the levels
of APP and expression of metallopeptidases involved in amyloid metabolism during all postnatal life and preconditioning to
hypoxia appeared to be neuroprotective. 相似文献
32.
We have investigated the role of zinc peptidases in metabolism of the amyloid precursor protein (APP) and the effects of hypoxia. Two peptidase families have been studied: the neprilysin (NEP) family which includes, in the brain: NEP, endothelin converting enzyme (ECE) and secreted endopeptidase (SEP). Reactive oxygen species can regulate enzyme activity via modulation of the zinc ion at the active site. Both NEP and ECE can prevent accumulation of amyloid beta peptide by hydrolyzing the peptide. As acute and chronic hypoxia can modulate APP processing, we have investigated the effects of hypoxia in cell culture on the expression and activity of NEP, ECE and SEP. In parallel, we have monitored the expression of another zinc peptidase, alpha-secretase, that mediates the nonamyloidogenic processing of APP. Overall, zinc peptidases appear neuroprotective and modulation of these activities in pathological states could lead to neurodegeneration.
Acknowledgements: This work was supported by the UK MRC, The Royal Society, INTAS, The Biochemical Society. 相似文献
Acknowledgements: This work was supported by the UK MRC, The Royal Society, INTAS, The Biochemical Society. 相似文献