Increased expression of signal proteins in mouse brain by withdrawal of nicotine after chronic administration of the alkaloid

We previously reported that nicotine withdrawal up-regulates transcription of some immediately early genes (IEGs), signal transduction-related genes, and apoptosis-related genes in cultures of pheochromocytoma PC12 cells, which are of neuronal lineage (Ichino et al., 1999; Ichino et al., 2002; Yamada et al., 2005). In the present study, we aimed at further elucidating the effects of nicotine withdrawal on the expression of the downstream proteins of IEGs in the brain from mice after the chronic administration of the alkaloid to them. We observed significant increases in the protein levels of Bag-1, Rab2, Hsp70, and Raf1 by Western blot analysis. The present results suggest that such changes may also occur in the brain of smokers during abstaining from smoking and may be related to their nicotine withdrawal symptoms.