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Mitogen‐activated protein kinase/extracellular signal‐regulated kinase attenuates 3‐hydroxykynurenine‐induced neuronal cell death
Author(s) -
Lee Hyun Jung,
Bach JaeHyung,
Chae HeeSun,
Lee Sang Hyung,
Joo Wan Seok,
Choi Se Hoon,
Kim Kyung Yong,
Lee Won Bok,
Kim Sung Su
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02191.x
Subject(s) - mapk/erk pathway , microbiology and biotechnology , programmed cell death , mitochondrion , protein kinase a , kinase , cytosol , extracellular , biology , apoptosis , mitogen activated protein kinase 3 , biochemistry , enzyme
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 (ΔΨ 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.