cDNA Microarray Analysis of Changes in Gene Expression Associated with MPP+ Toxicity in SH-SY5Y Cells |
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Authors: | Kelly J Conn M David Ullman Michelle J Larned Patricia B Eisenhauer Richard E Fine John M Wells |
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Institution: | (1) Department of Veterans Affairs, VA Medical Center, 200 Springs Road, Bedford, Massachusetts;(2) Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts;(3) Department of Psychiatry, Boston University School of Medicine, Boston, Massachusett;(4) University of Massachusetts Medical School, Waltham, Massachusetts;(5) Department of Neurology, Boston University School of Medicine, Boston, Massachusetts |
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Abstract: | cDNA microarray analysis of 1-methyl-4-phenyl-pyridinium (MPP+) toxicity (1 mM, 72 h) in undifferentiated SH-SY5Y cells identified 48 genes that displayed a signal intensity greater than the mean of all differentially expressed genes and a two-fold or greater difference in normalized expression. RT-PCR analysis of a subset of genes showed that c-Myc and RNA-binding protein 3 (RMB3) expression decreased by 50% after 72 h of exposure to MPP+ (1 mM) but did not change after 72 h of exposure to 6-hydroxydopamine (25 M), rotenone (50 nM), and hydrogen peroxide (600 M). Exposure of retinoic acid (RA)-differentiated SH-SY5Y cells to MPP+ (1 mM, 72 h) also resulted in a decrease in RMB3 expression and an increase in GADD153 expression. In contrast, c-Myc expression was slightly increased in RA-differentiated cells. Collectively, these data provide new insights into the molecular mechanisms of MPP+ toxicity and show that MPP+ can elicit distinct patterns of gene expression in undifferentiated and RA-differentiated SH-SY5Y cells. |
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Keywords: | cDNA microarray Parkinson's disease 1-methyl-4-phenyl-pyridinium gene expression neurodegeneration |
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