Oxidative DNA damage and reduced expression of DNA repair genes: Role in primary open angle glaucoma (POAG)

被引:24
作者
Mohanty, Kuldeep [1 ]
Dada, Rima [2 ]
Dada, Tanuj [1 ]
机构
[1] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ophthalmol, New Delhi 110029, India
[2] All India Inst Med Sci, Dept Anat, New Delhi, India
关键词
8-hydroxy-2-deoxyguanosine (8-OHdG); 8-oxoguanine DNA glycosylase (OGG1); glaucoma; oxidative stress; poly (ADP-ribose) polymerase 1 (PARP1); BASE EXCISION-REPAIR; NORMAL-TENSION GLAUCOMA; STRESS MARKERS; TRABECULAR MESHWORK; AQUEOUS-HUMOR; CELLS; ASSOCIATION; RISK; POLYMORPHISMS; MECHANISMS;
D O I
10.1080/13816810.2016.1261904
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Controversy exists regarding the role of oxidative DNA damage and DNA repair in primary open angle glaucoma (POAG). We performed a case control study to test the hypothesis that oxidative DNA damage and base excision repair (BER) genes PARP1 and OGG1 are involved in POAG pathogenesis.Materials and Methods: The study included 116 POAG patients and 116 cataract patients as controls. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA. RNA was extracted from blood by Trizol and converted to cDNA. The relative quantification of PARP1 and OGG1 genes normalized to -actin was calculated by the 2(-Ct) method. Comparisons between groups were done by student's t-test and correlation between parameters was seen by Pearson correlation coefficient. All p values less than 0.05 were considered significant.Results: Mean levels of 8-OHdG were (patients v/s controls) 19.53 1.40 vs. 15.0 +/- 2.6 ng/ml in plasma and 8.55 +/- 1.94 vs. 5.15 +/- 1.09 ng/ml in aqueous humor (p < 0.0001). Expression levels of PARP1 (0.44 +/- 0.05 vs. 0.88 +/- 0.04) and OGG1 (0.46 +/- 0.05 vs. 0.8 +/- 0.01) were significantly (p < 0.0001) less in the patients than controls. There was a significant negative correlation between the expression levels of PARP1 and OGG1 with plasma and aqueous 8-OHdG. There was a strong positive correlation between plasma and aqueous 8-OHdG levels.Conclusion: These results support our hypothesis that oxidative stress-induced DNA damage is associated with POAG. Increased oxidative DNA damage in POAG may be attributed to decreased expression of DNA repair enzymes of the BER pathway.
引用
收藏
页码:446 / 450
页数:5
相关论文
共 34 条
  • [1] Risk Factors for Primary Open Angle Glaucoma (POAG) Progression: A Study Ruled in Torino
    Actis, A. G.
    Versino, E.
    Brogliatti, B.
    Rolle, T.
    [J]. OPEN OPHTHALMOLOGY JOURNAL, 2016, 10 : 129 - 139
  • [2] Current concepts in the pathophysiology of glaucoma
    Agarwal, Renu
    Gupta, Suresh K.
    Agarwal, Puneet
    Saxena, Rohit
    Agrawal, Shyam S.
    [J]. INDIAN JOURNAL OF OPHTHALMOLOGY, 2009, 57 (04) : 257 - 266
  • [3] The role of DNA base excision repair in brain homeostasis and disease
    Akbari, Mansour
    Morevati, Marya
    Croteau, Deborah
    Bohr, Vilhelm A.
    [J]. DNA REPAIR, 2015, 32 : 172 - 179
  • [4] Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions
    Amouroux, Rachel
    Campalans, Anna
    Epe, Bernd
    Radicella, J. Pablo
    [J]. NUCLEIC ACIDS RESEARCH, 2010, 38 (09) : 2878 - 2890
  • [5] The Evaluation of the Oxidative Stress Parameters in Patients with Primary Angle-Closure Glaucoma
    Chang, Dong
    Sha, Qian
    Zhang, Xuefei
    Liu, Peipei
    Rong, Shengzhong
    Han, Tao
    Liu, Ping
    Pan, Hongzhi
    [J]. PLOS ONE, 2011, 6 (11):
  • [6] The role of base excision repair in the development of primary open angle glaucoma in the Polish population
    Cuchra, Magda
    Markiewicz, Lukasz
    Mucha, Bartosz
    Pytel, Dariusz
    Szymanek, Katarzyna
    Szemraj, Janusz
    Szaflik, Jerzy
    Szaflik, Jacek P.
    Majsterek, Ireneusz
    [J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2015, 778 : 26 - 40
  • [7] Impact of Single Nucleotide Polymorphisms of Base Excision Repair Genes on DNA Damage and Efficiency of DNA Repair in Recurrent Depression Disorder
    Czarny, Piotr
    Kwiatkowski, Dominik
    Toma, Monika
    Kubiak, Joanna
    Sliwinska, Agnieszka
    Talarowska, Monika
    Szemraj, Janusz
    Maes, Michael
    Galecki, Piotr
    Sliwinski, Tomasz
    [J]. MOLECULAR NEUROBIOLOGY, 2017, 54 (06) : 4150 - 4159
  • [8] Biomarkers of oxidative damage in human disease
    Dalle-Donne, I
    Rossi, R
    Colombo, R
    Giustarini, D
    Milzani, A
    [J]. CLINICAL CHEMISTRY, 2006, 52 (04) : 601 - 623
  • [9] Oxidative stress impairs the repair of oxidative DNA base modifications in human skin fibroblasts and melanoma cells
    Eiberger, Wolfgang
    Volkmer, Beate
    Amouroux, Rachel
    Dherin, Claudine
    Radicella, J. Pablo
    Epe, Bernd
    [J]. DNA REPAIR, 2008, 7 (06) : 912 - 921
  • [10] DNA repair mechanisms and their clinical impact in glioblastoma
    Erasimus, Helene
    Gobin, Matthieu
    Niclou, Simone
    Van Dyck, Eric
    [J]. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2016, 769 : 19 - 35