Nitric Oxide Metabolism
Nitric oxide (NO) is a biological signaling molecule that plays an important role in vascular regulation, immune responses, and neuronal signal transduction. The importance of NO as a biological signaling molecule was highlighted by a Nobel Prize in 1998, which was shared by a UCLA researcher, Dr. Louis Ignarro. This molecule is produced from the amino acid arginine in many cell types. The regulation of NO in physiological systems is complex and involves many aspects of its production and degradation. We are currently investigating the reactions of NO with hemoglobin in red blood cells, and have discovered novel mechanisms that regulate these reactions. This problem is crucial to the design of artificial blood substitutes and the treatment of cardiovascular diseases. This work contributes significantly to the fundamental understanding of the biological regulation of NO and the pathophysiology of NO related diseases.
Supplemental Information for Huang et al. PNAS 2001, 11771-11776
Erythrocyte Consumption of Nitric Oxide
Intravascular Flow Decreases Erythrocyte Consumption of Nitric Oxide
Mathematical Modeling of NO Diffusion and Reaction
El-Farra, N.H.;P. D. Christofides and J. C. Liao (2003) “Analysis of Nitric Oxide Transport Barriers in Blood Vessels Using a Distributed Multi-cellular Model” Annals of Biomed Engineering, Annals of Biomedical Engineering, Vol. 31, pp. 294–309
Liao, JC (2002) “Blood feud: Keeping hemoglobin from nixing NO”, Nature Medicine, 8: 1350-1351.
Han, T.H., Hyduke, D.R., Vaughn, M.W.,. Fukuto, J.M., and Liao, J.C. (2002) Nitric oxide reaction with red blood cells and hemoglobin under heterogeneous conditions. Proc. Natl. Acad. Sci. USA 99: 7763–7768.
Joshi, M.S., Ferguson, T.B., Han,T.H., Hyduke, D.R., Liao,J.C., Rassaf, T., Bryan, N., Feelisch, M., and Lancaster, J.R. (2002) Nitric Oxide is Consumed, Rather than Conserved, by Reaction with Oxyhemoglobin under Physiological Conditions. Proc. Natl. Acad. Sci. USA, 99:10341-6.
Huang, K.T.; Han, T. H.; Hyduke, D. R.; Vaughn, M. W.; Van Herle, H.; Hein, T. W.; Zhang, C.; Kuo, L.; and Liao, J.C. (2001) “Modulation of Nitric Oxide Bioavailability by Erythrocytes” Proc. Natl. Acad. Sci. USA. 98, 11771-11776
Chang, C.-I., J.C. Liao, and L. Kuo (2001) “Macrophage Arginase Promotes Tumor Cell Growth and Suppresses Nitric Oxide-Mediated Tumor Cytotoxicity, Cancer Research, 61, 1100-1106.
Vaughn, M.W., Kuang-Tse Huang, Lih Kuo, and J. C. Liao (2001), “Erythrocyte Consumption of Nitric Oxide: Competition Experiment and Model Analysis” Nitric Oxide Biology and Chemistry, 5, 18-31.
Hein, T.W., J. C. Liao, and L.Kuo (2000) “Oxidized LDL specifically impairs endothelium-dependent, nitric oxide-mediated dilation of coronary microvessels” Am. J. Physiol. Heart Circ. Physiol. 278:H175-H183.
Chang, C.I.; B. Zoghi; J. C. Liao; and L. Kuo (2000) “Interleukin-13 inhibits nitric oxide production through arginase induction in activated macrophages: Involvement of cAMP/PKA, tyrosine kinase, and p38 mitogen-activated protein kinase” J. Immunology. 165:2134-2141
J. C. Liao, T.W. Hein, M. W. Vaughn, K.T. Huang, and L. Kuo (1999) “ Intravascular Flow Decreases Erythrocyte Consumption of Nitric Oxide” Proc. Natl. Acad. Sci. USA, 96:8757-8761.
Vaughn, M.W., K.T Huang, L. Kuo, and J. C. Liao (1999) “Erythrocytes Possess an Intrinsic Barrier to Nitric Oxide Consumption” J. Biol. Chem. 275, 2342-2348.
Huang, K.T., Kuo, L. and J.C. Liao (1998) Lipopolysaccharide activates endothelial nitric oxide synthase through protein tyrosine kinase, Biochem. Biophys. Res. Comm. 245, 33-37.
Chang, C.I., J.C. Liao, and L. Kuo, (1998) “Arginase modulates nitric oxide production in activated macrophages” Am. J. Physiol. 274 (Heart Circ. Physiol.43): H342-348.
Vaughn, M.W., L. Kuo, and J.C. Liao (1998) "Effective diffusion distance of nitric oxide in microcirculation" Am.J. Physiol. 274:H1705-1714.
Vaughn, M.W., L. Kuo, and J.C. Liao (1998) “Estimation of nitric oxide production and reaction rates in tissue using a mathematical model" Am.J. Physiol. 274:H2163-H2176.
Liao, J.C., and L. Kuo. (1997) " Interaction between adenosine and flow-induced dilation in coronary microvascular network" Am. J. Physiol. (Heart Circ.Physiol. 41):H1571-H1581.