Heme Degradation and Vascular Injury
- 15 January 2010
- journal article
- review article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 12 (2), 233-248
- https://doi.org/10.1089/ars.2009.2822
Abstract
Heme is an essential molecule in aerobic organisms. Heme consists of protoporphyrin IX and a ferrous (Fe2+) iron atom, which has high affinity for oxygen (O2). Hemoglobin, the major oxygen-carrying protein in blood, is the most abundant heme-protein in animals and humans. Hemoglobin consists of four globin subunits (α2β2), with each subunit carrying a heme group. Ferrous (Fe2+) hemoglobin is easily oxidized in circulation to ferric (Fe3+) hemoglobin, which readily releases free hemin. Hemin is hydrophobic and intercalates into cell membranes. Hydrogen peroxide can split the heme ring and release “free” redox-active iron, which catalytically amplifies the production of reactive oxygen species. These oxidants can oxidize lipids, proteins, and DNA; activate cell-signaling pathways and oxidant-sensitive, proinflammatory transcription factors; alter protein expression; perturb membrane channels; and induce apoptosis and cell death. Heme-derived oxidants induce recruitment of leukocytes, platelets, and red blood cells to the vessel wall; oxidize low-density lipoproteins; and consume nitric oxide. Heme metabolism, extracellular and intracellular defenses against heme, and cellular cytoprotective adaptations are emphasized. Sickle cell disease, an archetypal example of hemolysis, heme-induced oxidative stress, and cytoprotective adaptation, is reviewed. Antioxid. Redox Signal. 12, 233–248.Keywords
This publication has 163 references indexed in Scilit:
- Quantitative real-time polymerase chain reaction (qRT-PCR) restriction fragment length polymorphism (RFLP) method for monitoring highly conserved transgene expression during gene therapyTranslational Research, 2008
- Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell VasculopathyJama-Journal Of The American Medical Association, 2008
- Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme OverloadThe American Journal of Pathology, 2008
- The proverbial chicken or the egg? Dissection of the role of cell-free hemoglobin versus reactive oxygen species in sickle cell pathophysiologyAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Redox-dependent impairment of vascular function in sickle cell diseaseFree Radical Biology & Medicine, 2007
- Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinasesCell Research, 2006
- Heme–thiolate proteinsBiochemical and Biophysical Research Communications, 2005
- Links Between Cell-Surface Events Involving Redox-Active Copper and Gene Regulation in the Hemopexin Heme Transport SystemAntioxidants and Redox Signaling, 2000
- Expression and modulatory effects of heme oxygenase in acute inflammation in the ratInflammation Research, 1995
- Hepatic subcellular metabolism of heme from heme-hemopexin: Incorporation of iron into ferritinBiochemical and Biophysical Research Communications, 1979