Laboratory of Pulmonary Molecular
Biology and Oxidative Stress

Duke University Medical Center

Molecular and Cellular Pathobiology of Antioxidant Enzymes

"My research group has long been interested in understanding the molecular and cellular biology of extracellular superoxide dismutase (EC-SOD) and uncovering its role in physiologic and pathophysiologic processes"

RJF

Description :
Antioxidant enzymes play pivotal roles during normal and pathological cellular processes. In
conditions of acute lung injury, the lungs are often exposed to elevated levels of oxygen and
infiltrating inflammatory cells. Such conditions are associated with elevated production of
reactive oxygen species (ROS), such as superoxide anions, hydrogen peroxide and hydroxyl
radicals. ROS can react with a host of biological molecules, altering their structure/function,
modulating signaling pathways and directly damaging cellular and tissue structures. My
laboratory has primarily been interested in understanding oxidant/antioxidant interactions in
the extracellular compartment. We have focused our inquiries on understanding the role of
extracellular antioxidants such as extracellular superoxide dismutase, glutathione peroxidase
and glutathione. These antioxidants collectively contribute to the bulk of the lungs extracellular
antioxidant reserves. We primarily utilize molecular biology techniques to critically test our
hypotheses primarily in models of acute oxidative lung injury. We are also interested in
understanding factors which regular antioxidant gene expression.

Publications by our Group:

Zelko, IN and RJ Folz. Extracellular superoxide dismutase functions as a major repressor of hypoxia-induced erythropoietin gene expression. Endocrinology, 146:332-340, 2005.

Rabbani ZN, MS Anscher, RJ Folz, E Archer, H Huang, L Chen, ML Golson, TS Samulski, MW Dewhirst, Z Vujaskovic. Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity. BMC Cancer, 5:59, 2005.

Park JW, WN Qi, JQ Liu, JR Urbaniak, RJ Folz, and LE Chen. Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice. Microsurgery, 25:606-613, 2005.

Park JW, WN Qi, Y Cai, I Zelko, JQ Liu, LE Chen, JR Urbaniak, RJ Folz. Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse. Am J Physiol Heart Circ Physiol, 289:H181-H187, 2005.

Zelko, IN and RJ Folz. Sp1 and Sp3 transcription factors mediate trichostatin A-induced and basal expression of extracellular superoxide dismutase. Free Radic Biol Med, 37:1256-1271, 2004.

Zelko, IN and RJ Folz. Myeloid zinc finger (MZF)-like, Kruppel-like and Ets families of transcription factors determine the cell-specific expression of mouse extracellular superoxide dismutase. Biochem J, 369:375-386, 2003.

Kang SK, ZN Rabbani, RJ Folz, ML Golson, H Huang, D Yu, TS Samulski, MW Dewhirst, MS Anscher, Z Vujaskovic. Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury. Int J Radiat Oncol Biol Phys, 57:1056-1066, 2003.

Ahmed, MN, HB Suliman, RJ Folz, E Nozik-Grayck, ML Golson, SN Mason, RL Auten. Extracellular superoxide dismutase protects lung development in hyperoxia-exposed newborn mice. Am J Respir Crit Care Med, 167: 400-405, 2003.

Nepluev I and RJ Folz. PACS RT-PCR: a method for the generation and measurement of any poly(A)-containing mRNA not affected by contaminating genomic DNA. Methods in Molecular Biology, 221:161-168, 2003.

Zelko, IN, TJ Mariani, RJ Folz. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med, 33:337-349, 2002.

Ghio, AJ, HB Suliman, JD Carter, AM Abushamaa, RJ Folz. Overexpression of extracellular superoxide dismutase decreases lung injury after exposure to oil fly ash. Am J Physiol Lung Cell Mol Physiol, 283:L211-L218, 2002.

Fukai, T, RJ Folz, U Landmesser, DG Harrison. Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc Res, 55:239-249, 2002.

Suliman HB, LK Ryan, L Bishop, RJ Folz. Prevention of influenza-induced lung injury in transgenic mice overexpressing extracellular superoxide dismutase. Am J Physiol Lung Cell Mol Physiol, 280:L69-L78, 2001.

Folz RJ and I Nepluev. Poly A cDNA-specific (PACS) RT-PCR: A quantitative method for the measurement of any poly A-containing mRNA not affected by contaminating genomic DNA. Biotechniques, 29:762-769, 2000.

Folz RJ, A Abushamaa, and HB Suliman. Extracellular superoxide dismutase in the airways of transgenic mice reduces inflammation and attenuates lung toxicity following hyperoxia. J Clin Invest, 103:1055-1066, 1999.

Chen EP, Bittner HB, Davis RD, Van Trigt P, RJ Folz. Physiologic effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury. J Thorac Cardiovasc Surg, 115:450-458, 1998.

Folz RJ, J Guan, MF Seldin, TD Oury, JJ Enghild, and JD Crapo. Mouse extracellular superoxide dismutase: primary structure, tissue-specific gene expression, chromosomal localization, and lung in situ hybridization. Am J Respir Cell Mol Biol, 17:393-403, 1997.

Folz RJ, JD Crapo, and LA Peno-Green. Elevated levels of extracellular SOD in chronic lung disease and characterization of genetic variants. Chest, 111:74S, 1997.

Suh, J-G, S Takai, T Yamanishi, T Kikuchi, RJ Folz, K Tanaka, Y-S Oh, K Wada. Sequence analysis, tissue expression and chromosomal localization of a mouse secreted superoxide dismutase gene. Molecules and Cells, 7:204-207, 1997.

Su W-Y, RJ Folz, J-S Chen, JD Crapo, and L-Y Chang. Extracellular superoxide dismutase mRNA expression in the human lung assessed by in situ hybridization. Am J Respir Cell Mol Biol, 16:162-170, 1997.

Folz RJ, CA Piantadosi, and JD Crapo. Oxygen Toxicity. In: The Lung: Scientific Foundations, Second Edition. RG Crystal and JB West (eds). Raven Press, New York, pp 2713-2722, 1996.

Chen EP, HB Bittner, F Tull, RD Davis, RJ Folz, and PV Trigt. Extracellular superoxide dismutase transgene overexpression preserves post-ischemic myocardial function in isolated murine hearts. Circulation, 94:412-417, 1996.

Folz RJ and JD Crapo. Pulmonary Oxygen Toxicity. In: Current Pulmonology. DF Tierney (ed). Mosby Year Book, Inc., Chicago, Volume 15, Chapter 4, pp 113-136, 1994.

Folz RJ, L Peno-Green, and JD Crapo. Identification of a homozygous missense mutation (Arg to Gly) in the critical binding region of the human EC-SOD gene (SOD3) and its association with dramatic increased serum enzyme levels. Human Molecular Genetics, 3:2251-2254, 1994.

Folz RJ and JD Crapo. Extracellular superoxide dismutase (SOD3): Tissue-specific expression, genomic characterization, and computer-assisted sequence analysis of the human EC-SOD gene. Genomics, 22:162-171, 1994.

Contact me by Email at rodney.folz at duke.edu
or snail mail at
Duke University Medical Center
Box 2620, Room 331 Medical Science Research Building
Durham, NC 27710
919-684-3539 (office)
919-681-8936 (fax)