Neuroprotective effects of overexpressed cyclophilin B against Aβ-induced neurotoxicity in PC12 cells.

Autor: Oh Y; Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, Biomedical Science Institute (BK-21), Kyung Hee University, Seoul 134-727, Korea., Kim EY, Kim Y, Jin J, Jin BK, Jahng GH, Jung MH, Park C, Kang I, Ha J, Choe W
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2011 Aug 15; Vol. 51 (4), pp. 905-20. Date of Electronic Publication: 2011 Jun 02.
DOI: 10.1016/j.freeradbiomed.2011.05.036
Abstrakt: Accumulated amyloid-β (Aβ) is a well-known cause of neuronal apoptosis in Alzheimer disease and functions in part by generating oxidative stress. Our previous work suggested that cyclophilin B (CypB) protects against endoplasmic reticulum (ER) stress. Therefore, in this study we examined the ability of CypB to protect against Aβ toxicity. CypB is present in the neurons of rat and mouse brains, and treating neural cells with Aβ(25-35) mediates apoptotic cell death. Aβ(25-35)-induced neuronal toxicity was inhibited by the overexpression of CypB as measured by cell viability, apoptotic morphology, sub-G1 cell population, intracellular reactive oxygen species accumulation, activated caspase-3, PARP cleavage, Bcl-2 proteins, mitogen-activated protein kinase (MAPK) activation, and phosphoinositide 3-kinase (PI-3-K) activation. CypB/R95A PPIase mutants did not reduce Aβ(25-35) toxicity. We showed that Aβ(25-35)-induced apoptosis is more severe in a CypB knockdown model, confirming that CypB protects against Aβ(25-35)-induced toxicity. Consequently, these findings suggest that CypB may protect against Aβ toxicity by its antioxidant properties, by regulating MAPK and PI-3-K signaling, and through the ER stress pathway.
(Copyright © 2011 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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