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Kynurenic acid attenuates MPP(+)-induced dopaminergic neuronal cell death via a Bax-mediated mitochondrial pathway.
Eur J Cell Biol. 2008 Jun; 87(6):389-97.EJ

Abstract

Kynurenic acid (KYNA), a tryptophan metabolite in the kynurenine pathway, is protective against various insults. However, the molecular mechanism of this protective effect has not been identified. In this study, we examined the protective effects of KYNA against 1-methyl-4-phenylpyridinium (MPP(+)), the best-characterized toxin inducing pathological changes resembling Parkinson's disease (PD), using SH-SY5Y and SK-N-SH human neuroblastoma cells. Pre-treatment of KYNA attenuated MPP(+)-induced neuronal cell death in SH-SY5Y and SK-N-SH cells. MPP(+)-induced cell death was preceded by increases in Bax expression and mitochondrial dysfunction, such as collapse of mitochondrial membrane potential (DeltaPsi(m)), release of cytochrome c from mitochondria into the cytoplasm, and increases in caspase-9/-3 activities. KYNA effectively inhibited all of these mitochondrial apoptotic processes. Our results indicate that KYNA plays a protective role by down-regulating Bax expression and maintaining mitochondrial function in MPP(+)-induced neuronal cell death, and suggest that KYNA may have therapeutic potential in PD.

Authors+Show Affiliations

Department of Anatomy and Cell Biology, College of Medicine, Chung-Ang University, Dongjak-Ku, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18462830

Citation

Lee, Do Yeon, et al. "Kynurenic Acid Attenuates MPP(+)-induced Dopaminergic Neuronal Cell Death Via a Bax-mediated Mitochondrial Pathway." European Journal of Cell Biology, vol. 87, no. 6, 2008, pp. 389-97.
Lee DY, Lee KS, Lee HJ, et al. Kynurenic acid attenuates MPP(+)-induced dopaminergic neuronal cell death via a Bax-mediated mitochondrial pathway. Eur J Cell Biol. 2008;87(6):389-97.
Lee, D. Y., Lee, K. S., Lee, H. J., Noh, Y. H., Kim, D. H., Lee, J. Y., Cho, S. H., Yoon, O. J., Lee, W. B., Kim, K. Y., Chung, Y. H., & Kim, S. S. (2008). Kynurenic acid attenuates MPP(+)-induced dopaminergic neuronal cell death via a Bax-mediated mitochondrial pathway. European Journal of Cell Biology, 87(6), 389-97. https://doi.org/10.1016/j.ejcb.2008.03.003
Lee DY, et al. Kynurenic Acid Attenuates MPP(+)-induced Dopaminergic Neuronal Cell Death Via a Bax-mediated Mitochondrial Pathway. Eur J Cell Biol. 2008;87(6):389-97. PubMed PMID: 18462830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kynurenic acid attenuates MPP(+)-induced dopaminergic neuronal cell death via a Bax-mediated mitochondrial pathway. AU - Lee,Do Yeon, AU - Lee,Kyu-Sun, AU - Lee,Hyun Jung, AU - Noh,Yoo Hun, AU - Kim,Do Hee, AU - Lee,Jun Young, AU - Cho,Soo Hyun, AU - Yoon,Ok Ja, AU - Lee,Won Bok, AU - Kim,Kyung Yong, AU - Chung,Yoon Hee, AU - Kim,Sung Su, Y1 - 2008/05/06/ PY - 2007/10/25/received PY - 2008/03/06/revised PY - 2008/03/10/accepted PY - 2008/5/9/pubmed PY - 2008/9/16/medline PY - 2008/5/9/entrez SP - 389 EP - 97 JF - European journal of cell biology JO - Eur J Cell Biol VL - 87 IS - 6 N2 - Kynurenic acid (KYNA), a tryptophan metabolite in the kynurenine pathway, is protective against various insults. However, the molecular mechanism of this protective effect has not been identified. In this study, we examined the protective effects of KYNA against 1-methyl-4-phenylpyridinium (MPP(+)), the best-characterized toxin inducing pathological changes resembling Parkinson's disease (PD), using SH-SY5Y and SK-N-SH human neuroblastoma cells. Pre-treatment of KYNA attenuated MPP(+)-induced neuronal cell death in SH-SY5Y and SK-N-SH cells. MPP(+)-induced cell death was preceded by increases in Bax expression and mitochondrial dysfunction, such as collapse of mitochondrial membrane potential (DeltaPsi(m)), release of cytochrome c from mitochondria into the cytoplasm, and increases in caspase-9/-3 activities. KYNA effectively inhibited all of these mitochondrial apoptotic processes. Our results indicate that KYNA plays a protective role by down-regulating Bax expression and maintaining mitochondrial function in MPP(+)-induced neuronal cell death, and suggest that KYNA may have therapeutic potential in PD. SN - 1618-1298 UR - https://www.unboundmedicine.com/medline/citation/18462830/Kynurenic_acid_attenuates_MPP_+__induced_dopaminergic_neuronal_cell_death_via_a_Bax_mediated_mitochondrial_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0171-9335(08)00061-7 DB - PRIME DP - Unbound Medicine ER -