Specific up-regulation of GADD153/CHOP in 1-methyl-4-phenyl-pyridinium-treated SH-SY5Y cells.
Growth arrest DNA damage-inducible 153 (GADD153) expression was increased in 1-methyl-4-phenyl-pyridinium (MPP(+))-treated human SH-SY5Y neuroblastoma cells as determined by gene microarray analysis. GADD153 expression increased after 24 hr of MPP(+) (1 mM) exposure and preceded activation of caspase 3. Comparison of GADD153 expression among cultures treated with other toxins whose primary mode of action is either via mitochondrial impairment (rotenone) or via oxidative stress (6-hydroxydopamine or hydrogen peroxide) showed that GADD153 was uniquely up-regulated by MPP(+). Together these data suggest that a cellular mechanism distinct from mitochondrial impairment or oxidative stress contributes significantly to the up-regulation of GADD153 by MPP(+) and that GADD153 may function as an inducer of apoptosis following MPP(+) exposure. Published 2002 Wiley-Liss, Inc.
Department of Veterans Affairs, VA Medical Center, Bedford, Massachusetts 01730, USA. conn.kelly_j@bedford.va.gov
Kelly J
KJ
Conn
Wen-Wu
WW
Gao
M David
MD
Ullman
Catherine
C
McKeon-O'Malley
Patricia B
PB
Eisenhauer
Richard E
RE
Fine
John M
JM
Wells
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology* / Q000633:toxicity; D018663:Adrenergic Agents / Q000494:pharmacology / Q000633:toxicity; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000032:analysis* / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006540:Herbicides / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology / Q000633:toxicity; D007306:Insecticides / Q000494:pharmacology / Q000633:toxicity; D009447:Neuroblastoma; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology / Q000633:toxicity; D016627:Oxidopamine / Q000494:pharmacology / Q000633:toxicity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012402:Rotenone / Q000494:pharmacology / Q000633:toxicity; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018663:Adrenergic Agents; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D006540:Herbicides; D007306:Insecticides; D016877:Oxidants; D012333:RNA, Messenger; D014157:Transcription Factors; D012402:Rotenone; D051742:Transcription Factor CHOP; D016627:Oxidopamine; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015655:1-Methyl-4-phenylpyridinium