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Heat shock proteins reduce toxicity of 1‐methyl‐4‐phenylpyridinium ion in SK‐N‐SH cells
Author(s) -
Fan GuoHua,
Qi Chen,
Chen ShengDi
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20656
Subject(s) - apoptosis , biology , oxidative stress , heat shock protein , substantia nigra , viability assay , microbiology and biotechnology , necrosis , neurotoxin , programmed cell death , reactive oxygen species , mptp , transfection , mitochondrion , neuroprotection , biochemistry , pharmacology , dopaminergic , endocrinology , gene , genetics , dopamine
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. © 2005 Wiley‐Liss, Inc.