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Heme oxygenase and cyclooxygenase in the central nervous system: A functional interplay
Author(s) -
Mancuso Cesare,
Perluigi Marzia,
Cini Chiara,
De Marco Carlo,
Giuffrida Stella Anna Maria,
Calabrese Vittorio
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21049
Subject(s) - heme oxygenase , biliverdin , heme , biliverdin reductase , chemistry , neuroprotection , biochemistry , cyclooxygenase , microbiology and biotechnology , pharmacology , biology , enzyme
Heme oxygenase (HO) and cyclooxygenase (COX) are two hemeproteins involved in the regulation of several functions in the nervous system. Heme oxygenase is the enzyme responsible for the degradation of heme into ferrous iron, carbon monoxide (CO), and biliverdin, the latter being further reduced in bilirubin (BR) by biliverdin reductase. Heme oxygenase‐derived CO is a gaseous neuromodulator and plays an important role in the synaptic plasticity, learning and memory processes, as well as in the regulation of hypothalamic neuropeptide release, whereas BR is an endogenous molecules with antioxidant and anti‐nitrosative activities. Cyclooxygenase is considered a pro‐inflammatory enzyme as free radicals and prostaglandins (PGs) are produced during its catalytic cycle. Although PGs are also involved in a variety of physiologic conditions including angiogenesis, hemostasis, or regulation of kidney function, upregulation of COX and increase in PGs levels are a common feature of neuroinflammation. In the brain, a functional interplay exists between HO and COX. Heme oxygenase regulates COX activity by reducing the intracellular heme content or by generating CO, which stimulates PGE 2 release. Increased levels of PGs, free radicals, and the associated oxidative stress serve in the brain as a trigger for the induction of HO isoforms which increases cellular antioxidant defenses to counteract oxidative damage. The importance of the interaction between HO and COX in the regulation of physiologic brain functions, and its relevance to neuroprotective or neurodegenerative mechanisms are discussed. © 2006 Wiley‐Liss, Inc.