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Toropygin IY Kugaevskaya EV Mirgorodskaya OA Elisseeva YE Kozmin YP Popov IA Nikolaev EN Makarov AA Kozin SA 《Rapid communications in mass spectrometry : RCM》2008,22(2):231-239
Chronic imbalance between production and degradation of the human amyloid-beta peptide (Abeta) is assumed to play an important role in pathogenesis of Alzheimer's disease (AD). Post-translational modifications of Abeta could influence its interactions with specifically cleaving proteases and, therefore, perturb the Abeta homeostasis. The angiotensin-converting enzyme (ACE) was previously shown to degrade non-modified Abeta in vitro and in cells. In the presented work, we investigated the effect of isomerization of Asp-7, a common non-enzymatic age-related modification found in AD-associated Abeta species, on hydrolysis of Abeta by ACE. Two synthetic peptides corresponding to the Abeta region 1-16 with either Asp or isoAsp residues in position 7 were examined as monomeric soluble substrates for the N- as well as for the C-domain of ACE. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) coupled with the (18)O-labeled internal standard approach has allowed us to show that (i) the N-domain of ACE (N-ACE), but not the C-domain, selectively cleaves the Arg-5-His-6 bond in both peptides, and that (ii) N-ACE hydrolyzes the isoAsp-7 analogue more efficiently than the non-modified one. Our results demonstrate a new endopeptidase activity of N-ACE as well as high preference of the domain to recognize and hydrolyze the isomerized Abeta species that were earlier suggested to promote AD pathogenesis. The results suggest the need for further analysis of biological effects of isomerized Abeta and its interaction with ACE in AD pathogenesis. 相似文献
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Subham Majumdar EV Sampathkumaran St Berger M Della Mea H Michor E Bauer M Brando J Hemberger A Loidl 《Pramana》2002,58(5-6):777-782
Recently, the solid solution Ce2Au1−
x
Co
xSi3 has been shown to exhibit many magnetic anomalies associated with the competition between magnetic ordering and the Kondo
effect. Here we report high pressure electrical resistivity of Ce2AuSi3, ac susceptibility (X) and magnetoresistance of various alloys of this solid solution in order to gain better knowledge of the magnetism of these
alloys. High pressure resistivity behavior is consistent with the proposal that Ce2AuSi3 lies at the left-hand side of the maximum in Doniach’s magnetic phase diagram. The ac X data reveal that there are in fact two magnetic transitions, one at 2 K and the other at 3 K for this compound, both of which
are spin-glass-like. However, as the Co concentration is increased, antiferromagnetism is stabilized for intermediate compositions
before attaining non-magnetism for the Co end member. 相似文献
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We have grown single crystals of the psuedo-one-dimensional compound Sr3CuIrO6, a K4CdCl6-derived monoclinic structure with Cu-Ir chains along the [101] direction. We present the ac and dc magnetization behavior
of the single crystals in comparison with that of the polycrystalline form reported earlier. There is a distinct evidence
for at least two magnetic transitions, at 5 K (T
1) and 19 K (T
2), with different relative magnitudes in the single and polycrystals. The low temperature magnetic relaxation behavior of
both the forms is found to be widely different, exhibiting unexpected time dependence. 相似文献
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