Heme degradation and vascular injury

Research output: Contribution to journalReview article

117 Citations (Scopus)

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 (α2β 2), with each subunit carrying a heme group. Ferrous (Fe 2+) hemoglobin is easily oxidized in circulation to ferric (Fe 3+) 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.

Original languageEnglish (US)
Pages (from-to)233-248
Number of pages16
JournalAntioxidants and Redox Signaling
Volume12
Issue number2
DOIs
StatePublished - Jan 15 2010

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Vascular System Injuries
Heme
Degradation
Hemoglobins
Oxidants
Hemin
Blood
Iron
Oxygen
Cell signaling
Hemeproteins
Proteins
Oxidative stress
Globins
Sickle Cell Anemia
Cell death
Cell membranes
Platelets
Hemolysis
Ion Channels

Cite this

Heme degradation and vascular injury. / Belcher, John D; Beckman, Joan D; Balla, Gyorgy; Balla, Jozsef; Vercellotti, Gregory M.

In: Antioxidants and Redox Signaling, Vol. 12, No. 2, 15.01.2010, p. 233-248.

Research output: Contribution to journalReview article

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