Polymorphisms of the CHRNA4 gene encoding the alpha4 subunit of nicotinic acetylcholine receptor as related to the oxidative DNA damage and the level of apoptotic proteins in lymphocytes of the patients with Alzheimer's disease.
The study aimed at the analysis of polymorphisms in the gene coding for the nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) and the evaluation of the extent of the oxidative damage to DNA (8-oxo2dG), as well as the level of proteins participating in DNA repair (p53, PARP) and DNA degradation (Bax:Bcl-2, 85-kDa fragment) in the peripheral blood lymphocytes of the patients suffering from Alzheimer's disease (AD) and in the healthy individuals of the control group. In the AD patients the increased levels of oxidized guanine were demonstrated in DNA, accompanied by the elevated expression of p53, Bax, PARP, and of a 85-kDa protein subunit as well as an augmented ratio of Bax:Bcl-2. Also, the level of Bcl-2 protein was decreased. In the AD patients with the CHRNA4 polymorphisms the highest level of 8-oxo2dG and of proteins involved in DNA repair were documented in patients with polymorphisms in exon 5, in contrast to the patients with polymorphisms in intron 5. In the former patients, levels of pro- and antiapoptotic proteins remained at the same level. Both CHRNA4 polymorphisms and the extent of dementia seem to affect the levels of DNA oxidative damage as well as to activate factors that participate in the DNA degradation and its repair.
Dorszewska
Jolanta
J
Laboratory of Neurobiology, Department of Neurology, University of Medical Sciences, Poznan, Poland. dorszewskaj@yahoo.com
Florczak
Jolanta
J
Rózycka
Agata
A
Jaroszewska-Kolecka
Joanna
J
Trzeciak
Wieslaw H
WH
Kozubski
Wojciech
W
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D024161:Collagen Type XI / Q000378:metabolism; D004249:DNA Damage; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000080242:8-Hydroxy-2'-Deoxyguanosine; D024161:Collagen Type XI; D017931:DNA Primers; D004268:DNA-Binding Proteins; D003849:Deoxyguanosine; D019253:Proto-Oncogene Proteins c-bcl-2; D011978:Receptors, Nicotinic; D051028:bcl-2-Associated X Protein; C499319:COL11A2 protein, human; C478985:PDRG1 protein, human