Impaired amyloid β-degrading enzymes in brain of streptozotocin-induced diabetic rats.
Enzymes that degrade the amyloid β-peptide (Aβ) are important regulators of cerebral Aβ levels. High level of Aβ was found in the brain of diabetic patients and diabetic animals. Aim of the study was to investigate whether activities of Aβ-degrading enzymes neprilysin (NEP), endothelin-converting enzyme 1 (ECE-1) and insulin-degrading enzyme (IDE) were impaired in the brain of diabetic rats. Diabetes was induced in rats by ip administration of 65 mg/kg streptozotocin. The temporal cortex and hippocampus were obtained for activity and mRNA level assays of the three enzymes on the 35th day after induction. ECE-1 activity was significantly decreased both in the hippocampus and cortex of diabetic rats, while for IDE significantly lower activity occurred only in the cortex. NEP activity was slightly decreased in both brain regions. The hippocampus of diabetic rats showed significant decrease in mRNA levels of NEP and ECE-1 and moderate increase in IDE mRNA level. The cortex of diabetic rats showed slight decrease in mRNA levels of the three enzymes. The results indicated that the three Aβ-degrading enzymes were damaged to different extents in the brain of diabetic rats, and impairment of ECE-1 and IDE partly contributed to the elevated Aβ(1-40) levels in brain of diabetic rats.
Liu
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Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Liu
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Lu
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Wang
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Liu
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Xie
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Wang
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D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000072396:Endothelin-Converting Enzymes; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D007339:Insulysin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015260:Neprilysin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D013311:Streptozocin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D007339:Insulysin; D000072396:Endothelin-Converting Enzymes