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SHR Neuro Cancer Cardio Lipid Metab Microb

Doberer, D; Haschemi, A; Andreas, M; Zapf, TC; Clive, B; Jeitler, M; Heinzl, H; Wagner, O; Wolzt, M; Bilban, M.
Haem arginate infusion stimulates haem oxygenase-1 expression in healthy subjects
BRIT J PHARMACOL. 2010; 161(8): 1751-1762. Doi: 10.1111/j.1476-5381.2010.00990.x
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Co-authors Med Uni Graz: Andreas Martin
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Abstract:: BACKGROUND AND PURPOSE Haem oxygenase 1 (HO-1) is an inducible protein that plays a major protective role in conditions such as ischaemia-reperfusion injury and inflammation. In this study, we have investigated the role of haem arginate (HA) in human male subjects in the modulation of HO-1 expression and its correlation with the GT length polymorphism (GT(n)) in the promoter of the HO-1 gene. EXPERIMENTAL APPROACH In a dose-escalation, randomized, placebo-controlled trial, seven healthy male subjects with a homozygous short (S/S) and eight with a long (L/L) GT(n) genotype received intravenous HA. HO-1 protein expression and mRNA levels in peripheral blood monocytes, bilirubin, haptoglobin, haemopexin and haem levels were analysed over a 48 h observation period. KEY RESULTS We found that the baseline mRNA levels of HO-1 were higher in L/L subjects, while protein levels were higher in S/S subjects. HA induced a dose-dependent increase in the baseline corrected area under the curve values of HO-1 mRNA and protein over 48 h. The response of HO-1 mRNA was more pronounced in L/L subjects but the protein level was similar across the groups. CONCLUSIONS AND IMPLICATION HA is an effective inducer of HO-1 in humans irrespective of the GT(n) genotype. The potential therapeutic application of HA needs to be evaluated in clinical trials.
Find related publications in this database (Keywords): haem oxygenase; ischaemia-reperfusion injury; healthy volunteers; polymorphism