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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.