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Heat shock proteins reduce toxicity of 1-methyl-4-phenylpyridinium ion in SK-N-SH cells.
J Neurosci Res. 2005 Nov 15; 82(4):551-62.JN

Abstract

The pathology of Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the pathogenesis of PD remains unclear. Heat shock proteins (HSPs) have many functions, including inhibition of apoptosis and necrosis, protection from oxidative stress, and maintenance of the mitochondrial membrane potential, that are related to neurodegenerative diseases. 1-Methyl-4-phenylpyridinium ion (MPP(+)) is a neurotoxin that selectively inhibits the mitochondrial functions of DA neurons in the substantia nigra. MPP(+) administration is accepted as a model for PD. In the present study, we found that MPP(+) induced a concentration- and time-dependent decrease in cell viability. Lower concentrations of MPP(+) induced mainly early apoptosis, and, as the concentration increased, the number of late apoptotic and necrotic cells significantly increased. However, treated by heat shock preconditioning or transfection with HDJ-1, a homologue of human Hsp40, cells showed marked improvement in viability after exposure to the same concentrations of MPP(+). Compared with heat shock, HDJ-1 appeared to improve cell viability obviously. Similarly, HDJ-1 elicited significantly stronger protective effects against apoptosis and necrosis. In addition, HDJ-1 transfection maintained more injured cells in early apoptotic stages and inhibited the occurrence of late apoptotic/necrotic events. Heat shock and HDJ-1 both ameliorated MPP(+)-induced cytotoxicity by maintaining the mitochondrial membrane potential and reducing reactive oxygen species (ROS). Therefore, the effects of HSPs, such as reducing apoptosis and necrosis, preserving mitochondrial functions and decreasing oxidative stress, may bring a novel approach for PD therapy.

Authors+Show Affiliations

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Second Medical University, China.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16235253

Citation

Fan, Guo-Hua, et al. "Heat Shock Proteins Reduce Toxicity of 1-methyl-4-phenylpyridinium Ion in SK-N-SH Cells." Journal of Neuroscience Research, vol. 82, no. 4, 2005, pp. 551-62.
Fan GH, Qi C, Chen SD. Heat shock proteins reduce toxicity of 1-methyl-4-phenylpyridinium ion in SK-N-SH cells. J Neurosci Res. 2005;82(4):551-62.
Fan, G. H., Qi, C., & Chen, S. D. (2005). Heat shock proteins reduce toxicity of 1-methyl-4-phenylpyridinium ion in SK-N-SH cells. Journal of Neuroscience Research, 82(4), 551-62.
Fan GH, Qi C, Chen SD. Heat Shock Proteins Reduce Toxicity of 1-methyl-4-phenylpyridinium Ion in SK-N-SH Cells. J Neurosci Res. 2005 Nov 15;82(4):551-62. PubMed PMID: 16235253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heat shock proteins reduce toxicity of 1-methyl-4-phenylpyridinium ion in SK-N-SH cells. AU - Fan,Guo-Hua, AU - Qi,Chen, AU - Chen,Sheng-Di, PY - 2005/10/20/pubmed PY - 2006/2/17/medline PY - 2005/10/20/entrez SP - 551 EP - 62 JF - Journal of neuroscience research JO - J Neurosci Res VL - 82 IS - 4 N2 - The pathology of Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the pathogenesis of PD remains unclear. Heat shock proteins (HSPs) have many functions, including inhibition of apoptosis and necrosis, protection from oxidative stress, and maintenance of the mitochondrial membrane potential, that are related to neurodegenerative diseases. 1-Methyl-4-phenylpyridinium ion (MPP(+)) is a neurotoxin that selectively inhibits the mitochondrial functions of DA neurons in the substantia nigra. MPP(+) administration is accepted as a model for PD. In the present study, we found that MPP(+) induced a concentration- and time-dependent decrease in cell viability. Lower concentrations of MPP(+) induced mainly early apoptosis, and, as the concentration increased, the number of late apoptotic and necrotic cells significantly increased. However, treated by heat shock preconditioning or transfection with HDJ-1, a homologue of human Hsp40, cells showed marked improvement in viability after exposure to the same concentrations of MPP(+). Compared with heat shock, HDJ-1 appeared to improve cell viability obviously. Similarly, HDJ-1 elicited significantly stronger protective effects against apoptosis and necrosis. In addition, HDJ-1 transfection maintained more injured cells in early apoptotic stages and inhibited the occurrence of late apoptotic/necrotic events. Heat shock and HDJ-1 both ameliorated MPP(+)-induced cytotoxicity by maintaining the mitochondrial membrane potential and reducing reactive oxygen species (ROS). Therefore, the effects of HSPs, such as reducing apoptosis and necrosis, preserving mitochondrial functions and decreasing oxidative stress, may bring a novel approach for PD therapy. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/16235253/Heat_shock_proteins_reduce_toxicity_of_1_methyl_4_phenylpyridinium_ion_in_SK_N_SH_cells_ L2 - https://doi.org/10.1002/jnr.20656 DB - PRIME DP - Unbound Medicine ER -