Mitogen-activated protein kinase/extracellular signal-regulated kinase attenuates 3-hydroxykynurenine-induced neuronal cell death
- Authors
- Lee, Hyun Jung; Bach, Jae-Hyung; Chae, Hee-Sun; Lee, Sang Hyung; Joo, Wan Seok; Choi, Se Hoon; Kim, Kyung Yong; Lee, Won Bok; Kim, Sung Su
- Issue Date
- Feb-2004
- Publisher
- BLACKWELL PUBLISHING LTD
- Keywords
- apoptosis; extracellular signal-regulated kinase; 3-hydroxykynurenine; mitochondrial malfunction
- Citation
- JOURNAL OF NEUROCHEMISTRY, v.88, no.3, pp 647 - 656
- Pages
- 10
- Journal Title
- JOURNAL OF NEUROCHEMISTRY
- Volume
- 88
- Number
- 3
- Start Page
- 647
- End Page
- 656
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24880
- DOI
- 10.1046/j.1471-4159.2003.02191.x
- ISSN
- 0022-3042
1471-4159
- Abstract
- 3-Hydroxykynurenine (3-HK), an endogenous tryptophan metabolite, is known to have toxic effects in brain. However, the molecular mechanism of the toxicity has not been well identified. In this study, we investigated the involvement of MAPK/extracellular signal-regulated kinase (ERK) in the 3-HK-induced neuronal cell damage. Our results showed that 3-HK induced apoptotic neuronal cell death and ERK phosphorylation occurred during cell death. Inhibition of ERK activation using PD98059 considerably increased cell death. Furthermore, cell death was preceded by mitochondrial malfunction including collapse of mitochondrial membrane potential (DeltaPsi(m)) and cytochrome c release from mitochondria to the cytosol. Interestingly, inhibition of ERK dramatically increased mitochondrial malfunction, and enhanced caspase activation, resulting in enhanced neuronal cell death. Thus, our results show that ERK plays a protective role by maintaining mitochondrial function and regulating caspase activity under conditions of cellular stress.
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