Hepatitis C virus induces oxidative stress and DNA damage by regulating DNAPKCs, ATM, ATR and PARP mediated signaling and guards cell from cancerous condition by upregulating RB, P53 and downregulating VEGF

Abstract

Hepatitis C virus is responsible for liver damage and various metabolic disorders. HCV infections promote oxidative stress and cause damage to macromolecules. The aim of our study was to design a preliminary study with establishment of HCV genotype 3a infectivity assay in order to determine DNA damage in Huh-7 cell line at 72 hours post inoculation. Quantitative expression levels of COX-2 and GSR (oxidants and antioxidants), DNAPKCs, ATM, ATR and PARP (DNA damage and repair genes), RB and P53 (tumor suppressor genes) and VEGF (angiogenesis marker) were observed via real time PCR. Our findings revealed 1.533 fold upregulated expression of COX-2. The expression level of GSR was increased by1.27 fold and VEGF expression decreased by 0.367 fold. Thus, preventing cells to enter cancerous phase.

Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients

“…Two possible explanations for the non-significant changes in TAOs among all groups are: 1) induction of antioxidant mechanisms because of the disease to counteract the generated oxidative stressors, and 2) the increases in the highly antioxidant bilirubin in patients. TAOs and MDA showed a significant negative correlation in HCV-NE patients similar to previous studies [6,9,11,28]. In the cirrhotic patients, there was a positive significant correlation between TAOs and total peroxides.…”

“…One pathogenic mechanism for HCV is oxidative stress resultant from increased generation of reactive oxygen species in infected hepatocytes, where redox homeostatic balance is a major challenge to prevent cell death and DNA mutation [4][5][6][7][8]. Mechanistically, HCV activates prooxidant enzymes and hepatic stellate cells, weakens antioxidant defenses, and induces organelle damage, secretion of pro-inflammatory cytokines and metals unbalance -secondary to mitochondrial failure, which is a focal point in that scenario [9,10]. The early induced oxidative stress is responsible for HCV liver disease progression towards both steatosis and fibrosis [9].…”

“…Mechanistically, HCV activates prooxidant enzymes and hepatic stellate cells, weakens antioxidant defenses, and induces organelle damage, secretion of pro-inflammatory cytokines and metals unbalance -secondary to mitochondrial failure, which is a focal point in that scenario [9,10]. The early induced oxidative stress is responsible for HCV liver disease progression towards both steatosis and fibrosis [9].…”

“…Their inducibility is orchestrated by the transcription regulator, the hypoxia-inducible factor-1α (HIF-1α) [17][18][19][20]. HCV infections promote oxidative stress, while downregulating VEGF mRNA expression very early after infection that rebounds in the long term [9]. The marked variability in VEGF and sVEGFR concentrations in HCV-induced hepatic disease makes them weak indicators for the progression of chronic liver disease in cirrhotic patients.…”

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

“…As a result, the antioxidant defense system may be significantly perturbed. Thus, it was found that the level of glutathione-disulfide reductase was significantly reduced in the red blood cells isolated from individuals with human immunodeficiency virus infection [149] or, on the contrary, was increased in Huh-7 cell line infected with HCV [150]. 15 NEDD4 33 NEDD4 (neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase) gene encodes E3 ubiquitin-protein ligase NEDD4.…”