Iron and transferrrin uptake by brain and cerebrospinal fluid in the rat

Crowe, Andrew; Morgan, Evan H.

doi:10.1016/0006-8993(92)91652-u

Cited by 147 publications

(128 citation statements)

References 25 publications

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“…DETC alone can penetrate the blood-brain barrier, but Fe ions may not (Crowe and Morgan, 1992). Therefore, it seems unlikely that the Fe-DETC complex is formed in the brain parenchyma.…”

Section: Discussionmentioning

confidence: 99%

Electron Paramagnetic Resonance (EPR) Detection of Nitric Oxide Produced during Forebrain Ischemia of the Rat

Tominaga¹,

Sato

Ohnishi

et al. 1994

J Cereb Blood Flow Metab

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Summary: To detect if nitric oxide (NO) is produced in rat forebrain ischemia, we applied an electron paramag netic resonance (EPR) NO-trapping technique. We also performed a detailed characterization of the technique. Diethyldithiocarbamate (DETC) and Fe-citrate were used as NO-trapping reagents. Under controlled ventilation, forebrain ischemia was produced by occlusion of both carotid arteries combined with hemorrhagic hypotension at 50 mm Hg for 15 min. DETC and Fe were administered 30 min prior to the onset of ischemia. During ischemia, the cerebral cortex was removed, and EPR samples were prepared. At liquid nitrogen temperatures, the NO-Fe DETC signal (a triplet signal centered at g = 2.039 with the hyperfine coupling constant aN of 13 G) was detected Nitric oxide (NO) is a highly reactive regulatory molecule with a wide range of distribution through out the body, including the brain. Based upon its physiological role, the major sources of NO produc tion in the brain are thought to be endothelial cells and neurons (Palmer et al., 1988;Moncada et al., 1991;Bredt and Snyder, 1992). NO or a related compound released from endothelial cells serves as an endothelium-derived relaxing factor that main tains and regulates vascular tone (Moncada et al., 1991; Vanin, 1991;Prado et al., 1992 Abbreviations used: CCA, common carotid artery; DEA/NO, 1,I-diethyl-2-hydroxy-2-nitrosohydrazine; DETC, diethyldithio carbamate; EPR, electron paramagnetic resonance; Hb, hemo globin; L-NAME, N-nitro-L-arginine methyl ester; NMDA, N-methyl-o-aspartate; NOS, nitric oxide synthase. 715overlapping Cu-DETC signals. By perfusing various con centrations of an NO-generating agent, 1, I-diethyl-2-hy droxy-2-nitrosohydrazine, into the rat brains, the amount of the "trapped NO" was calibrated. The size of the NO Fe-DETC signal was well correlated with the NO con centrations in the perfusate (correlation coefficient r = 0.998, P < 0.01). Based on this calibration curve, it was found that the amount of trapped NO during forebrain ischemia increased to seven times that of the control (control n = 5, forebrain ischemia n = 4, P < 0.005). Key Words: Brain ischemia-Diethyldithiocarbamate-l, 1-Di ethyl-2-hydroxy-2-nitrosohydrazine-Electron paramag netic resonance-Nitric oxide-Nitric oxide trapping.1992; Buchanan and Phillis, 1993;Pelligrino et al. , 1993). The neuronal production of NO is evidenced by the fact that a constitutive NO synthase (NOS) exists in neurons throughout the brain Vincent and Kimura, 1992;Nozaki et al., 1993). NO acts as an intraneuronal and interneu ronal messenger by activating soluble guanylate cy clase and by blocking the N-methyl-o-aspartate (NMDA) receptor (Knowles et al., 1989; Garth waite, 1991;Bredt and Snyder, 1992;Lei et al., 1992;Manzoni et al., 1992). NO is a free radical, and its short half-life «30 s) has rendered direct measurement difficult. To demonstrate the produc tion of NO indirectly, the levels of nitrite sjnitrates, stable metabolites of NO, and cyclic GMP have been measured. Alternatively, NOS inhibi...

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“…DETC alone can penetrate the blood-brain barrier, but Fe ions may not (Crowe and Morgan, 1992). Therefore, it seems unlikely that the Fe-DETC complex is formed in the brain parenchyma.…”

Section: Discussionmentioning

confidence: 99%

Electron Paramagnetic Resonance (EPR) Detection of Nitric Oxide Produced during Forebrain Ischemia of the Rat

Tominaga¹,

Sato

Ohnishi

et al. 1994

J Cereb Blood Flow Metab

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“…Both iron and copper are absorbed by the cells of the choroid plexus and through enterocytes of the proximal portion of the duodenum, and copper has also been shown to be absorbed in the stomach. 9,[22][23][24] Therefore, the expression profile combined with the functional data of Steap2 raises the possibility that it is a metalloreductase in these tissues specifically promoting iron and copper uptake.…”

Section: Discussionmentioning

confidence: 99%

The Steap proteins are metalloreductases

Ohgami

Campagna

McDonald

et al. 2006

Blood

558

532

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Iron and copper are essential for all organisms, assuming critical roles as cofactors in many enzymes. In eukaryotes, the transmembrane transport of these elements is a highly regulated process facilitated by the single electron reduction of each metal. Previously, we identified a mammalian ferrireductase, Steap3, critical for erythroid iron homeostasis. Now, through homology, expression, and functional studies, we characterize all 4 members of this protein family and demonstrate that 3 of them, Steap2, Steap3, and Steap4, are not only ferrireductases but also cupric reductases that stimulate cellular uptake of both iron and copper in vitro. Finally, the pattern of tissue expression and subcellular localization of these proteins suggest they are physiologically relevant cupric reductases and ferrireductases in vivo. (Blood. 2006;108:1388-1394

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“…The CNS uses its own transferrin whose expression is regulated by a CNS specific promoter [12,13]. Regarding iron storage, ferritin binds and stores intracellular iron in most CNS cells, keeping it in a redox-inactive state [14].…”

Section: Introductionmentioning

confidence: 99%

Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease

et al. 2007

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Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. AD in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.

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Iron and transferrrin uptake by brain and cerebrospinal fluid in the rat

Cited by 147 publications

References 25 publications

Electron Paramagnetic Resonance (EPR) Detection of Nitric Oxide Produced during Forebrain Ischemia of the Rat

Electron Paramagnetic Resonance (EPR) Detection of Nitric Oxide Produced during Forebrain Ischemia of the Rat

The Steap proteins are metalloreductases

Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease

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