and/or aims): During the previous funding period, the applicant demonstrated that heme oxygenase is a key enzyme in heme metabolism and purified that enzyme to homogeneity; partially sequenced it; prepared antibodies to it and has begun to use antibodies as a tool to quantify HO levels in many tissues. In this renewal proposal, the applicant proposes to extend his previous studies of HO by; further analysis of the HO protein; improvement of the immunochemical analysis for HO which he has developed; cloning, sequencing and characterizing the structural gene coding for HO starting with a cDNA library; cloning of the 5' cis-acting HO regulatory sequences from a genomic library; analyzing the regulation of HO gene expression at the levels of transcription and translation during physiologically relevant states with particular reference to fetal-adult phenotypes; studying the mechanism whereby zinc (Zn++) prevents the potentiating effect of iron on uroporphyrin accumulation by liver cell cultures; and exploring the effects of clinically relevant drugs, metals, energy substrates and hormones on key enzymes of heme metabolism.
| Bonkovsky, Herbert L; Hou, Weihong; Steuerwald, Nury et al. (2013) Heme status affects human hepatic messenger RNA and microRNA expression. World J Gastroenterol 19:1593-601 |
| Larion, Sebastian; Caballes, Frederick R; Hwang, Sun-Il et al. (2013) Circadian rhythms in acute intermittent porphyria--a pilot study. Eur J Clin Invest 43:727-39 |
| Maddukuri, Vinaya C; Russo, Mark W; Ahrens, William A et al. (2013) Chronic hepatitis E with neurologic manifestations and rapid progression of liver fibrosis in a liver transplant recipient. Dig Dis Sci 58:2413-6 |
| Bonkovsky, Herbert L; Guo, Jun-Tao; Hou, Weihong et al. (2013) Porphyrin and heme metabolism and the porphyrias. Compr Physiol 3:365-401 |
| Thapar, Manish; Covault, Jonathan; Hesselbrock, Victor et al. (2012) DNA methylation patterns in alcoholics and family controls. World J Gastrointest Oncol 4:138-44 |
| Ryan Caballes, F; Sendi, Hossein; Bonkovsky, Herbert L (2012) Hepatitis C, porphyria cutanea tarda and liver iron: an update. Liver Int 32:880-93 |
| Hou, Weihong; Tian, Qing; Steuerwald, Nury M et al. (2012) The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes. Biochim Biophys Acta 1819:1113-22 |
| Lakner, Ashley M; Bonkovsky, Herbert L; Schrum, Laura W (2011) microRNAs: fad or future of liver disease. World J Gastroenterol 17:2536-42 |
| Li, Ting; Bonkovsky, Herbert L; Guo, Jun-tao (2011) Structural analysis of heme proteins: implications for design and prediction. BMC Struct Biol 11:13 |
| Rakoski, Mina O; Brown, Morton B; Fontana, Robert J et al. (2011) Mallory-Denk bodies are associated with outcomes and histologic features in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 9:902-909.e1 |
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