Polymorphisms of theCHRNA4Gene Encoding the α4 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

Abstract

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.

Original article A transcript coding for a partially duplicated form of α7 nicotinic acetylcholine receptor is absent from the CD4 + T-lymphocytes of patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

“…Our investigations A transcript coding for a partially duplicated form of α7 nicotinic acetylcholine receptor is absent from the CD4 + T-lymphocytes of patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) support the involvement of the α4 subunit of nAChR in this process [11]. Increased levels of the CHRNA7 transcript in the hippocampus, as well as in the lymphocytes, of AD patients have been reported [19,20], suggesting that the elevation in CHRNA7 gene expression may be associated with AD, and that the receptors localized in PBLs correspond to the same receptors in the brain.…”

Lipidomic fatty acid profile and global gene expression pattern in mammary gland of rats that were exposed to lard-based high fat diet during fetal and lactation periods associated to breast cancer risk in adulthood

“…Chrna4 encodes a nicotinic acetylcholine receptor which participates in the predisposition for preneoplastic lesions and emergence of lung carcinomas [56]. On the other hand, silent polymorphism in exon 5 in Chrna4 is associated to high levels oxidative DNA damage [57]. Additional studies are needed to evaluate the significance of these connections and the possible effects on mammary tumorigenesis.…”

Increased T-cell Reactivity and Elevated Levels of CD8+ Memory T-cells in Alzheimer’s Disease-patients and T-cell Hyporeactivity in an Alzheimer’s Disease-mouse Model: Implications for Immunotherapy

“…There are numerous reports concerning changes in T-cells from AD patients concerning distribution (Singh 1990;Pirttila et al 1992;Shalit et al 1995;Lombardi et al 1999;Tan et al 2002;Schindowski et al 2006) and function including altered basal expression of activation markers (Ikeda et al 1991a, b;Shalit et al 1995;Bongioanni et al 1997b;Lombardi et al 1999), disturbed Calcium homeostasis (Adunsky et al 1991;Grossmann et al 1993;Adunsky et al 1995;Eckert et al 1995;Ibarreta et al 1997;Palotas et al 2002), altered cytokine secretion (Shalit et al 1995;Bongioanni et al 1997aBongioanni et al , b, 1998Monsonego et al 2003;Sala et al 2003;Iarlori et al 2005;Galimberti et al 2006;Rota et al 2006), impaired proliferation (Shalit et al 1995;Lombardi et al 1999;Stieler et al 2001), and increased apoptosis (Lombardi et al 1999;Maesaka et al 1999;Eckert et al 2001a;Panossian et al 2003;Schindowski et al 2003;Dorszewska et al 2005;Frey et al 2006;Schindowski et al 2006). Remarkably, Ab stimulates lymphocytes from healthy donors, however, lymphocytes from AD patients do not respond upon Ab exposure (Eckert et al 1995;Trieb et al 1996) reflecting hyporeactivit...…”