Decreased activity of the antioxidant heme oxygenase enzyme: implications in ischemia and in Alzheimer's disease.
Heme oxygenase (HO) is the rate-limiting enzyme for the degradation of heme, a prooxidant, coming from a multitude of heme-containing proteins/enzymes. With the action of cytochrome P(450) reductase, HO cleaves the heme ring into biliverdin which is converted into bilirubin, both have been shown to have intrinsic radical scavenger activities. Iron is also released from the heme core and in its free form can act as a catalyst for oxidative stress damage or can be sequested by several iron-binding proteins. Under physiological conditions, the newly generated iron can be neutralized within the cell. The third product of the opening of the porphyrin ring is carbon monoxide, which role has been puzzling. It has been reported as a potential neuromodulator, it modulates guanylate cyclase activity and has vasodilation, anti-inflammatory and antiapoptotic effects. In the brain, HO2 accounts for the vast majority of HO activity. By decreasing HO2 activity, one would expect more neuronal damage after oxidative stress injury with possible direct implications to acute and chronic neurodegenerative disorders. Pharmacological ways to increase neuronal HO activity is likely to have therapeutic applications.
Doré
Sylvain
S
Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA. sd@jhmi.edu
D000544:Alzheimer Disease / Q000201:enzymology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002545:Brain Ischemia / Q000201:enzymology*; D015536:Down-Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans
D000975:Antioxidants; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2