A pathway of neuronal apoptosis induced by hypoxia/reoxygenation: roles of nuclear factor-kappaB and Bcl-2.
Journal Article (Journal Article)
As a model of the reperfusion injury found in stroke, we have exposed neurons to hypoxia followed by reoxygenation. Neurons treated with hypoxia/reoxygenation (H/R) respond by activating nuclear factor-kappaB (NFkappaB), releasing cytochrome c from their mitochondria, and ultimately dying. Further supporting an apoptotic mechanism, expression of the antiapoptotic Bcl-2 and Bcl-x proteins was increased following H/R. In this model, adenoviral-mediated transduction of lkappaB expression inhibited NFkappaB activation and significantly accelerated cytochrome c release and caspase-dependent neuronal death. At the same time, expression of mutated lkappaB prevented the increased expression of endogenous Bcl-2 and Bcl-x. In the presence of mutated lkappaB, singular overexpression of only Bcl-2 by adenoviral-mediated transduction significantly inhibited cytochrome c release, caspase-3-like activation, and cell death in response to H/R. These findings suggest a pathway where NFkappaB activation induces overexpression of Bcl-2 and Bcl-x, which function to prevent apoptotic cell death following H/R treatments.
Full Text
Duke Authors
Cited Authors
- Tamatani, M; Mitsuda, N; Matsuzaki, H; Okado, H; Miyake, S; Vitek, MP; Yamaguchi, A; Tohyama, M
Published Date
- August 2000
Published In
Volume / Issue
- 75 / 2
Start / End Page
- 683 - 693
PubMed ID
- 10899943
International Standard Serial Number (ISSN)
- 0022-3042
Digital Object Identifier (DOI)
- 10.1046/j.1471-4159.2000.0750683.x
Language
- eng
Conference Location
- England