Sealy Center for Molecular Medicine

Research Interests

Oxidative stress is due to reactive oxygen species (ROS), which are generated endogenously and continuously induced by environmental pollutants. Intracellularly, ROS is generated by activated intracellular oxidases due to inflammation, infections and drug treatment. Although a variety of cellular processes have evolved to eliminate ROS, oxidative stress occurs when there is a serious imbalance between production of ROS and antioxidant defense. Mitochondria are the major source of ROS and are present in all eukaroytic cells, from hundreds to thousands performing multiple cellular functions and are the major source of cellular energy. In mitochondria, ROS are formed by the univalent reduction of molecular oxygen that is mediated by respiratory complexes and via reactive compounds such as semi-ubiquinone. The long-term goal of Boldogh's laboratory is to use multidisciplinary approaches to understand the basic mechanisms by which mitochondrial ROS is generated and are etiological agents in aging, age-related diseases and as well as augment antigen-induced allergic inflammations. Dr. Boldogh is the director of The Cell Biology Core Laboratory (CBCL) at the National Institute of Environmental Health and Sciences (NIEHS) Center at UTMB. The CBCL is dedicated to the development and delivery of state-of-the-art methods and technologies in cell biology to assist NIEHS Center Investigators in their mission. A wide range of diseases is included in the Center investigators' research programs, such as cancer, drug abuse, behavioral disorders, chronic inflammatory lung diseases, aging and age-associated diseases. Related research ranges from studies of molecules (damaged DNA, DNA repair proteins, transcription factors, drug metabolism and interactions) and cells to those of whole animals and human populations. In addition to state-of-the-art equipment and methods, the key personnel of this core provide scientific and technical expertise that greatly benefits Center investigators in terms of experimental design, execution and interpretation.

Selected Publications

1. Hegde ML, Banerjee S, Hegde PM, Bellot LJ, Hazra TK, Boldogh I, Mitra S. Enhancement of NEIL1 Protien-initiated Ozidized DNA Base Excision Repair by Heterogeneous Nuclear Ribonucleoprotien U (hnRNP-U) via Direct Interaction. J Biol Chem. 287(41):34202-11, 2012; PMID: 22902625; PMCID: PMC3464528
   
   
2. G Hajas, A. Bacsi, ML. Hegde, TK. Hazra, S. Sur, Z. Radak, X. Ba, and I. Boldogh  8-Oxoguanine DNA glycosylase-1 links DNA repair to cellular responses via the activation of the small GTPase Rac1.  Free Radical Biology and Medicine, FRBM-D-12-01016; 2012
   
   
3. Hegde, ML., PM. Hegde, D. Arijit, I. Boldogh, S. Mitra  Human DNA Glycosylase NEIL1's Interactions with Downstream Repair Proteins Is Critical for Efficient Repair of Oxidized DNA Base Damage and Enhanced Cell Survival.  Biomolecules, No biomolecules-24982, In press 2012
   
   
4. Bacsi, A. L. Aguilera-Agurre, ML. Hegde, TK .Hazra, S. Sur, Z. Radak, X. Ba, and I. Boldogh  Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation. DNA Repair. No. DNAREP1720, In press, 2012
   
   
5. Mandal SM, Hegde ML, Chatterjee A., Hedge P., Szczesny B., Banerjee D, Boldogh I. Gao, R., Falkenberg, C., Sarkar PS, Hazra TK. The role of DNA glycosylases NEIL2 and the single strand break protein polynucleotide kinase 3'-phosphatase in maintenance of the mitochondrial genome. J Biol Chem. 287(4):2819-29, 2012 PMID: 22130663; PMCID: PMC3268439
   
   
6. Hajas, G. A Bacsi, P. German, Z. Radak, TK. Hazra, and I. Boldogh  Biochemical identification of a hydroperoxide derivative of the free 8-oxo-7,8-dihydroguanine base. Free Radical Biology and Medicine,  52(4):749-56, 2012 PMID: 22198182
   
   
7. Murai, H., Choudhury, B, Qi, H., Wild, J. Dharajiya, N., Vaidya, S., Kalita, A., Bacsi, A, Corry, D., Kurosky, A, Brasier, A, Boldogh, I., and Sur, S. Alternaria-induced release of IL-18 from damaged airway epithelial cells: An NF-kB dependent mechanism of Th2 differentiation. PloS ONE, 2012;7(2):e30280 2012; PMID: 22347372; PMCID: PMC3274547
   
   
8. Mandal SM, Hegde ML, Chatterjee A, Hegde PM, Szczesny B, Banerjee D, Boldogh I, Gao R, Falkenberg M, Gustafsson CM, Sarkar PS, Hazra TK. Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome. J Biol.Chem.287(4): 2819-29, 2012. PMID: 22130663; PMCID: PMC3268439
   
   
9. Dey S, Maiti AK, Hegde ML, Hegde PM, Boldogh I, Sarkar PS, Abdel-Rahman SZ, Sarker AH, Hang B, Xie J, Tomkinson AE, Zhou M, Shen B, Wang G, Wu C, Yu D, Lin D, Cardenas V, Hazra TK. Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2. DNA Repair (Amst). 11(6):570-8 2012 PMID: 22497777; PMCID: PMC3361577
   
   
10. Boldogh, I., Hajas, G., L. Aguilera-Aguirre, ML. Hegde, Z. Radak, A Bacsi, S. Sur, TK. Hazra, and S. Mitra. Activation of Ras Signaling by 8-oxoguanine DNA Glycosylase Bound to Its Excision Product 8-oxoguanine. *Corresponding Author, J Biol Chem. 287, 20769-20773, 2012; PMID: 22568941; PMCID: PMC3375501
    
    
11. Noriegil-Cisneros, R., Ortiz-Av ila, O., Esquivel-Gutierrez, E., Clemente-Guerrero, M., Salvador Mal1zo-Ava los, S., Salgado-Garciglia, R., Cortes-Rojo, C. I. Boldogh, Saavedra-Molina, A.  Hypolipidemic activity of Eryngium carlinae on streptozotocin-induced diabetic rats.  Biochem. Res. International 2012, 1-5, 2011 doi: 10.1155 /2012/603501 PMID 603501
    
    
12. Pazmandi, K., I. Boldogh, Z. Magyarics, A. Csillag; E. Rajnavolgyi, A. Bacsi.  Modulatory effects of low-dose exogenous hydrogen peroxide on the function of human plasmacytoid dendritic cells, Free Radical Biology and Medicine 52(3):635-45, 2012 PMID: 22178414
    
    
13. Koltai, E., Z. Zhao, Z. Lacza, A. Cselenyak, G. Vacz, C. Nyakas, I. Boldogh, N. Ichinoseki-Sekine, and Z. Radak. Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage.  Rejuvenation Research, 14(6): 585-596, 2012, PMID: 21867412; PMCID: PMC3239321
    
    
14. Bori, Z., Zhao, Z., Koltai, E., Fatouros, I.G., Jamurtas, A.Z., Fouroudos, I.I., Terzis, F., Chatzinikolaou, A., Sovatzidis, A., Draganidis, D., Boldogh, I., Radak, Z. The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle.  Exp Gerontology. 47(6):417-24. 2012 
    
    
15. Banerjee D, Mandal SM, Das A, Hegde ML, Das S, Bhakat KK, Boldogh I, Sarkar PS, Mitra S, Hazra TK Preferential repair of oxidized base damage in the transcribed genes of mammalian cells. J Biol Chem. 286(8):6006-16, 2011 PMID: 21169365
    
    
16. Tann AW, Boldogh I, Meiss G, Qian W, Van Houten B, Mitra S, Szczesny B  Apoptosis induced by persistent single-strand breaks in the mitochondrial genome: Critical role of EXOG (5' EXO/Endonuclease) in their repair.  J Biol Chem. 286(37):31975-83, 2011; PMID: 21768646; PMCID: PMC3173182
    
    
17. Yadav, U., Aguilera-Aguirre, L. Boldogh, I. Ramana, KV., Srivastava, SK.  Aldose reductase deficiency in mice protects from ragweed pollen extract-induced allergic asthma, Respiratory Research  Nov 3;12:145, 2011; PMID: 22054012
    
    
18. Radak, Z. Z. Bori, E. Koltai, I.G. Fatouros, A.Z. Jamurtas, I.I. Douroudos, G. Terzis, M.G. Nikolaidis, A. Chatzinikolaou, A. Sovatzidis, S. Kumagai, H. Naito, I. Boldogh.  Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle.  Free Radical Biology and Medicine 51(2):417-23. 2011 PMID: 21569841
    
    
19. Gutierrez-Perez A, Cortes-Rojo C, Noriega-Cisneros R, Calderon-Cortes E, Manzo-Avalos S, Clemente-Guerrero M, Boldogh I, Saavedra-Molina A. Protective effects of resveratrol on calcium-induced oxidative stress in rat heart mitochondria.  J Bioenerg Biomembr. 1 43(2):101-7. 2011 PMID: 21448653
    
    
20. Cortes-Rojo C, Estrada-Villagomez M, Calderon-Cortes E, Clemente-Guerrero M, Mejia-Zepeda R, Boldogh I, Saavedra-Molina A.  Electron transport chain dysfunction by H(2)O (2) is linked to increased reactive oxygen species production and iron mobilization by lipoperoxidation: studies using Saccharomyces cerevisiae mitochondria.  J Bioenerg Biomembr. 43(2):135-47. 2011, PMID:  21350953
    
    
21. Koltai, E., Zhao, Z, Lacza, Cselenyak, A., Vacz, G., Nyakas, Cs., Boldogh, I., Ichinoseki-Sekine, N., Zs. Radak  Combined exercise and IGF-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage. Rejuvenation Research, 14(6):585-96, 2011 PMID: 21867412; PMCID: PMC3239321
    
    
22. Boldogh, I., BK. Choudhury, TK. Hazra, R. Alam, R. Goldblum, S. Mitra and S. Sur. Oxidative stress generated by pollen NADPH oxidases provide a second signal that augments antigen-induced allergic inflammation. J. Clinical Investigations, 115:2169-2179, 2005.
    
    
23. Bacsi, A., Choudhury, B.K., Dharajiya, N., Sur, S., and Boldogh, I. Impact of pollen-mediated oxidative stress on hypersensitivity reactions and lat-phase inflammation in allergic conjunctivitis. J. Allergy & Clinical Immunology, 116:836-43, 2005.
    
    
24. Choudhary S, Boldogh I, Garofalo R, Jamaluddin M, Brasier AR. Respiratory syncytial virus influences NF-kappaB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-kappaB2. Journal of Virology 79:8948-8959, 2005.
25. Das, A., Boldogh, I., Hazra, T., Bhakat K., and Mitra, S. Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species. J Biol Chem. 280(42):35272-35280, 2005.
26. Bacsi, A. Kannan, S. Myung-Soog Lee Hazra, TK., and Boldogh, I. Modulation of Kinase Activity of DNA-PK in Chlorambucil-Treated Cells. Free Rad Biol. Med. 39:1650-1659, 2005.
27. Ray, S., I. Boldogh, and A.R., Brasier. STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen. Gastroenterology, 129:1616-1632, 2005.
28. BK., Mokkapati, SK., Boldogh, I., Hazra, TK., and Mitra, S. Acetylation of human 8-oxoguanine-DNA glycosylases by p300 and its role in 8-oxoxguanine repair in vivo. Mol. Cell Biol., 26: 1654-1665, 2006.
29. Das, G., Bacsi, A., M. Srivastaw, Hazra, TK. and Boldogh, I. Enhanced ?-glutamylcysteine synthetase activity ameliorates drug-induced oxidative stress levels and cytotoxicity. Molecular Carcinogenesis, 45:635-647, 2006.
30. Chattopadhyay R, Wiederhold L, Szczesny B, Boldogh I, Hazra TK, Izumi T, Mitra S. Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells. Nucleic Acids Res. 34:2067-2076, 2006.
31. Forbus, J., H. Spratt, J. Wiktorowicz, Z. Wu, I. Boldogh, L. Denner, A. Kurosky, R.C. Brasier, B. Luxon and A.R. Brasier. Functional analysis of the nuclear proteome of human A549 alveolar epithelial cells by HPLC-high resolution 2D gel electrophoresis. Proteomics, 6:2656-2672, 2006.
32. Kruzel, ML., A. Bacsi, B. Choudhury, S. Sur, and I. Boldogh. Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology 119:159-166, 2006.
33. Bacsi, A., M. Woodberry, W. Widger, J. J.W. Peterson, Papaconstantinou and I. Boldogh, Localization of Superoxide Anion Production to Mitochondrial Electron Transport Chain in 3-NPA-Treated Cells. Mitochondrion, 6:235-244, 2006.
34. Bacsi, A., B.K. Choudhury, N. Dharajiya, S. Sur, I. Boldogh, Sub-pollen particles: carriers of allergens and oxidases. J. Allergy & Clinical Immunology 118:844-850, 2006.