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Antidepressants reveal differential effect against 1-methyl-4-phenylpyridinium toxicity in differentiated PC12 cells.
Eur J Pharmacol. 2009 Feb 14; 604(1-3):36-44.EJ

Abstract

Treatment of depression may ameliorate the cognitive disability and motor slowness in Parkinson's disease. It has been shown that antidepressants, including fluoxetine, may attenuate or exacerbate neuronal cell death. The present study assessed the effect of antidepressants (amitriptyline, tranylcypromine and fluoxetine) against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in relation to the mitochondria-mediated cell death process in differentiated PC12 cells. Amitriptyline and tranylcypromine attenuated the MPP(+)-induced cell death that may be associated with mitochondrial membrane permeability change and oxidative stress. Both compounds prevented the loss of the mitochondrial transmembrane potential, over-expression of Bax, reduction in Bcl-2 level, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH. The inhibitory effect of tranylcypromine was greater than that of amitriptyline on the basis of concentration. In contrast, fluoxetine revealed a toxic effect and exhibited an additive effect against the toxicity of MPP(+). Results show that amitriptyline and tranylcypromine may attenuate the MPP(+) toxicity by suppressing the mitochondrial membrane permeability change that leads to cytochrome c release and subsequent caspase-3 activation. The effects seem to be associated with the inhibitory action on the formation of reactive oxygen species and the depletion of GSH. In contrast, fluoxetine seems to exert an additive toxic effect against neuronal cell damage by increasing mitochondrial damage and oxidative stress.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19135049

Citation

Han, Young Su, and Chung Soo Lee. "Antidepressants Reveal Differential Effect Against 1-methyl-4-phenylpyridinium Toxicity in Differentiated PC12 Cells." European Journal of Pharmacology, vol. 604, no. 1-3, 2009, pp. 36-44.
Han YS, Lee CS. Antidepressants reveal differential effect against 1-methyl-4-phenylpyridinium toxicity in differentiated PC12 cells. Eur J Pharmacol. 2009;604(1-3):36-44.
Han, Y. S., & Lee, C. S. (2009). Antidepressants reveal differential effect against 1-methyl-4-phenylpyridinium toxicity in differentiated PC12 cells. European Journal of Pharmacology, 604(1-3), 36-44. https://doi.org/10.1016/j.ejphar.2008.12.025
Han YS, Lee CS. Antidepressants Reveal Differential Effect Against 1-methyl-4-phenylpyridinium Toxicity in Differentiated PC12 Cells. Eur J Pharmacol. 2009 Feb 14;604(1-3):36-44. PubMed PMID: 19135049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressants reveal differential effect against 1-methyl-4-phenylpyridinium toxicity in differentiated PC12 cells. AU - Han,Young Su, AU - Lee,Chung Soo, Y1 - 2008/12/24/ PY - 2008/07/12/received PY - 2008/11/30/revised PY - 2008/12/11/accepted PY - 2009/1/13/entrez PY - 2009/1/13/pubmed PY - 2009/6/25/medline SP - 36 EP - 44 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 604 IS - 1-3 N2 - Treatment of depression may ameliorate the cognitive disability and motor slowness in Parkinson's disease. It has been shown that antidepressants, including fluoxetine, may attenuate or exacerbate neuronal cell death. The present study assessed the effect of antidepressants (amitriptyline, tranylcypromine and fluoxetine) against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in relation to the mitochondria-mediated cell death process in differentiated PC12 cells. Amitriptyline and tranylcypromine attenuated the MPP(+)-induced cell death that may be associated with mitochondrial membrane permeability change and oxidative stress. Both compounds prevented the loss of the mitochondrial transmembrane potential, over-expression of Bax, reduction in Bcl-2 level, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH. The inhibitory effect of tranylcypromine was greater than that of amitriptyline on the basis of concentration. In contrast, fluoxetine revealed a toxic effect and exhibited an additive effect against the toxicity of MPP(+). Results show that amitriptyline and tranylcypromine may attenuate the MPP(+) toxicity by suppressing the mitochondrial membrane permeability change that leads to cytochrome c release and subsequent caspase-3 activation. The effects seem to be associated with the inhibitory action on the formation of reactive oxygen species and the depletion of GSH. In contrast, fluoxetine seems to exert an additive toxic effect against neuronal cell damage by increasing mitochondrial damage and oxidative stress. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19135049/Antidepressants_reveal_differential_effect_against_1_methyl_4_phenylpyridinium_toxicity_in_differentiated_PC12_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)01259-4 DB - PRIME DP - Unbound Medicine ER -