HO-1 overexpression and underexpression: Clinical implications

• Published in: Archives of biochemistry and biophysics 2019-09, Vol.673, p.108073-108073, Article 108073
• Main Authors: Drummond, George S., Baum, Jeffrey, Greenberg, Menachem, Lewis, David, Abraham, Nader G.
• Format: Article
• Language: English
• Subjects: Adipocyte inflammation; adipocytes; Animals; Bilirubin; Disease; Fatty liver; Gene Expression Regulation, Enzymologic; heme; Heme - metabolism; heme oxygenase (biliverdin-producing); Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; Hyperbilirubinemia; Hypertension; jaundice; lipids; metabolic syndrome; Obesity; oxidative stress; Signal Transduction
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2019.108073

In this review we examine the effects of both over- and under-production of heme oxygenase-1 (HO-1) and HO activity on a broad spectrum of biological systems and on vascular disease. In a few instances e.g., neonatal jaundice, overproduction of HO-1 and increased HO activity results in elevated levels of bilirubin requiring clinical intervention with inhibitors of HO activity. In contrast HO-1 levels and HO activity are low in obesity and the HO system responds to mitigate the deleterious effects of oxidative stress through increased levels of bilirubin (anti-inflammatory) and CO (anti-apoptotic) and decreased levels of heme (pro-oxidant). Site specific HO-1 overexpression diminishes adipocyte terminal differentiation and lipid accumulation of obesity mediated release of inflammatory molecules. A series of diverse strategies have been implemented that focus on increasing HO-1 and HO activity that are central to reversing the clinical complications associated with diseases including, obesity, metabolic syndrome and vascular disease.