Nicotine modulates expression of amyloid precursor protein and amyloid precursor-like protein 2 in mouse brain and in SH-SY5Y neuroblastoma cells.
Epidemiological studies indicate that tobacco smoking can be protective against neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The objective of the present study was to examine the changes in gene expression induced by chronic oral nicotine administration (100 mug/ml in 2% saccharin for 14 days), with special emphasis on amyloid precursor protein (APP) and its homologue, amyloid precursor-like protein 2 (APLP2), in different brain regions of C57BL/6 mice using a pathway-focused microarray. Our results revealed that nicotine stimulated mRNA expression of APP in the amygdala (64%; P = 0.003) and hippocampus (32%; P = 0.034) and of APLP2 in the amygdala (39%; P = 0.002). These results were verified by quantitative real-time RT-PCR except that expression of APLP2 was also significantly upregulated by nicotine in the hippocampus. In addition, in vitro nicotine treatment of SH-SY5Y neuroblastoma cells resulted in a significant increase in expression of APP protein, soluble APP, and APLP2, whereas co-treatment with mecamylamine (an antagonist of nicotinic acetylcholine receptors) attenuated the stimulating effect of nicotine on APP and APLP2 expression. These findings suggest that nicotine treatment facilitates the increase in the expression of mRNA and protein of the APP and APLP2 genes in rat brain and SH-SY5Y neuroblastoma cells.
Gutala
Ramana
R
Department of Psychiatric Medicine, Section of Neurobiology, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, USA.
Wang
Ju
J
Hwang
Yoon Y
YY
Haq
Riaz
R
Li
Ming D
MD
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D009538:Nicotine