Increased oxidative stress as a risk factor in chronic idiopathic axonal polyneuropathy

Chronic idiopathic axonal polyneuropathy (CIAP) is a disorder with insidious onset and slow progression, where no etiology is identified despite appropriate investigations. We aimed to investigate the role of oxidative stress as a risk factor for the pathogenesis of CIAP. Sera of patients with CIAP were tested for protein carbonyl (PC) and 8-hydroxydeoxyguanosine (8H). As a control group, we recruited patients with gluten neuropathy. Twenty-one patients with CIAP and 21 controls were recruited. The two groups did not differ significantly regarding demographics or clinical characteristics (i.e., neuropathy type or disease severity). After adjusting for gender, having CIAP was positively correlated with both the 8H titer (standardized beta coefficient 0.349, p = 0.013) and the PC titer (standardized beta coefficient 0.469, p = 0.001). Oxidative stress appears to be increased in CIAP and might have a role in the pathogenesis of the disease

An in silico study of the differential effect of oxidation on two biologically relevant G-quadruplexes: Possible implications in oncogene expression

G-quadruplex structures, formed from guanine rich sequences, have previously been shown to be involved in various physiological processes including cancer-related gene expression. Furthermore, G-quadruplexes have been found in several oncogene promoter regions, and have been shown to play a role in the regulation of gene expression. The mutagenic properties of oxidative stress on DNA have been widely studied, as has the association with carcinogenesis. Guanine is the most susceptible nucleotide to oxidation, and as such, G-rich sequences that form G-quadruplexes can be viewed as potential "hot-spots" for DNA oxidation. We propose that oxidation may destabilise the G-quadruplex structure, leading to its unfolding into the duplex structure, affecting gene expression. This would imply a possible mechanism by which oxidation may impact on oncogene expression. This work investigates the effect of oxidation on two biologically relevant G-quadruplex structures through 500 ns molecular dynamics simulations on those found in the promoter regions of the c-Kit and c-Myc oncogenes. The results show oxidation having a detrimental effect on stability of the structure, substantially destabilising the c-Kit quadruplex, and with a more attenuated effect on the c-Myc quadruplex. Results are suggestive of a novel route for oxidation-mediated oncogenesis and may have wider implications for genome stability