PMID- 20074151
OWN - NLM
STAT- MEDLINE
DCOM- 20100816
LR  - 20211020
IS  - 1440-1746 (Electronic)
IS  - 0815-9319 (Print)
IS  - 0815-9319 (Linking)
VI  - 25
IP  - 3
DP  - 2010 Mar
TI  - Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA 
      repair enzyme NEIL1.
PG  - 627-34
LID - 10.1111/j.1440-1746.2009.06128.x [doi]
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV)-induced chronic inflammation may 
      induce oxidative stress which could compromise the repair of damaged DNA, 
      rendering cells more susceptible to spontaneous or mutagen-induced alterations, 
      the underlying cause of liver cirrhosis and hepatocellular carcinoma. In the 
      current study we examined the induction of reactive oxygen species (ROS) 
      resulting from HCV infection and evaluated its effect on the host DNA damage and 
      repair machinery. METHODS: HCV infected human hepatoma cells were analyzed to 
      determine (i) ROS, (ii) 8-oxoG and (iii) DNA glycosylases NEIL1, NEIL2, OGG1. 
      Liver biopsies were analyzed for NEIL1. RESULTS: Human hepatoma cells infected 
      with HCV JFH-1 showed 30-60-fold increases in ROS levels compared to uninfected 
      cells. Levels of the oxidatively modified guanosine base 8-oxoguanine (8-oxoG) 
      were significantly increased sixfold in the HCV-infected cells. Because DNA 
      glycosylases are the enzymes that remove oxidized nucleotides, their expression 
      in HCV-infected cells was analyzed. NEIL1 but not OGG1 or NEIL2 gene expression 
      was impaired in HCV-infected cells. In accordance, we found reduced glycosylase 
      (NEIL1-specific) activity in HCV-infected cells. The antioxidant N-acetyl cystein 
      (NAC) efficiently reversed the NEIL1 repression by inhibiting ROS induction by 
      HCV. NEIL1 expression was also partly restored when virus-infected cells were 
      treated with interferon (IFN). HCV core and to a lesser extent NS3-4a and NS5A 
      induced ROS, and downregulated NEIL1 expression. Liver biopsy specimens showed 
      significant impairment of NEIL1 levels in HCV-infected patients with advanced 
      liver disease compared to patients with no disease. CONCLUSION: Collectively, the 
      data indicate that HCV induction of ROS and perturbation of NEIL1 expression may 
      be mechanistically involved in progression of liver disease and suggest that 
      antioxidant and antiviral therapies can reverse these deleterious effects of HCV 
      in part by restoring function of the DNA repair enzyme/s.
FAU - Pal, Sampa
AU  - Pal S
AD  - Department of Laboratory Medicine, University of Washington, Seattle, Washington 
      98195-7110 USA. sampa@u.washington.edu
FAU - Polyak, Stephen J
AU  - Polyak SJ
FAU - Bano, Nazneen
AU  - Bano N
FAU - Qiu, Wan Chong
AU  - Qiu WC
FAU - Carithers, Robert L
AU  - Carithers RL
FAU - Shuhart, Margaret
AU  - Shuhart M
FAU - Gretch, David R
AU  - Gretch DR
FAU - Das, Aditi
AU  - Das A
LA  - eng
GR  - R01 AI049168/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20100114
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (Reactive Oxygen Species)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (NEIL1 protein, human)
RN  - EC 6.5.1.- (DNA Ligases)
SB  - IM
MH  - Biopsy
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/pathology/virology
MH  - *DNA Damage
MH  - DNA Glycosylases/*metabolism
MH  - DNA Ligases
MH  - Disease Progression
MH  - Hepacivirus/metabolism/*pathogenicity
MH  - Humans
MH  - Liver Cirrhosis/genetics/*metabolism/pathology/virology
MH  - Liver Neoplasms/genetics/*metabolism/pathology/virology
MH  - Mutation
MH  - *Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
PMC - PMC3565844
MID - NIHMS434390
EDAT- 2010/01/16 06:00
MHDA- 2010/08/17 06:00
PMCR- 2013/02/06
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/08/17 06:00 [medline]
PHST- 2013/02/06 00:00 [pmc-release]
AID - JGH6128 [pii]
AID - 10.1111/j.1440-1746.2009.06128.x [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2010 Mar;25(3):627-34. doi: 
      10.1111/j.1440-1746.2009.06128.x. Epub 2010 Jan 14.