cDNA microarray analysis of changes in gene expression associated with MPP+ toxicity in SH-SY5Y cells.
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 approximately 50% after 72 h of exposure to MPP+ (1 mM) but did not change after 72 h of exposure to 6-hydroxydopamine (25 microM), rotenone (50 nM), and hydrogen peroxide (600 microM). 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.
Conn
Kelly J
KJ
Department of Veterans Affairs, VA Medical Center, 200 Springs Road, Bedford, Massachusetts 01730, USA. kconn@bu.edu
Ullman
M David
MD
Larned
Michelle J
MJ
Eisenhauer
Patricia B
PB
Fine
Richard E
RE
Wells
John M
JM
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D014212:Tretinoin; D015655:1-Methyl-4-phenylpyridinium