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Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine.
Ann N Y Acad Sci. 2004 Oct; 1025:267-73.AN

Abstract

The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.

Authors+Show Affiliations

Research and Development, Sigma-tau HealthScience S.p.A., Pomezia 00040, Italy. ashraf.virmani@st-hs.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15542726

Citation

Virmani, Ashraf, et al. "Role of Mitochondrial Dysfunction in Neurotoxicity of MPP+: Partial Protection of PC12 Cells By Acetyl-L-carnitine." Annals of the New York Academy of Sciences, vol. 1025, 2004, pp. 267-73.
Virmani A, Gaetani F, Binienda Z, et al. Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine. Ann N Y Acad Sci. 2004;1025:267-73.
Virmani, A., Gaetani, F., Binienda, Z., Xu, A., Duhart, H., & Ali, S. F. (2004). Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine. Annals of the New York Academy of Sciences, 1025, 267-73.
Virmani A, et al. Role of Mitochondrial Dysfunction in Neurotoxicity of MPP+: Partial Protection of PC12 Cells By Acetyl-L-carnitine. Ann N Y Acad Sci. 2004;1025:267-73. PubMed PMID: 15542726.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine. AU - Virmani,Ashraf, AU - Gaetani,Franco, AU - Binienda,Zbigniew, AU - Xu,Alex, AU - Duhart,Helen, AU - Ali,Syed F, PY - 2004/11/16/pubmed PY - 2005/2/19/medline PY - 2004/11/16/entrez SP - 267 EP - 73 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 1025 N2 - The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/15542726/Role_of_mitochondrial_dysfunction_in_neurotoxicity_of_MPP+:_partial_protection_of_PC12_cells_by_acetyl_L_carnitine_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2004&volume=1025&spage=267 DB - PRIME DP - Unbound Medicine ER -