of work: This project focuses on the mechanism involved in regulating the binding of oxygen to hemoglobin and the transport of oxygen to the tissues. Emphasis is placed on ways in which these functions are impaired and change with age. These studies have focused on the oxidation of hemoglobin, which produces nonfunctional hemoglobin and the simultaneous release of oxyradicals. The enhancement of these oxidative processes under hypoxic conditions is being explored as a possible source of tissue and organ damage, which would be exacerbated during aging. Studies are also included which are directed at the stability of the entire erythrocyte and the erythrocyte membrane. Animal and human studies are performed to investigate possible functional impairment associated with red cell damage. Erythrocyte nitric oxide is being studied as a measure of nitric oxide synthesis and nitrite reduction in order to oxplore the possible role of the erythrocyte in regulating blood flow by releasing nitric oxide. The interaction of amyloids with the erythrocyte is being investigated to determine whether the red cell plays a role in the transport of amyloids and in amyloid induced oxidative stress.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000047-37
Application #
7591959
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
37
Fiscal Year
2007
Total Cost
$814,389
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Rifkind, Joseph M; Nagababu, Enika; Barbiro-Michaely, Efrat et al. (2007) Nitrite infusion increases cerebral blood flow and decreases mean arterial blood pressure in rats: a role for red cell NO. Nitric Oxide 16:448-56
Nagababu, Enika; Ramasamy, Somasundaram; Rifkind, Joseph M (2007) Intermediates detected by visible spectroscopy during the reaction of nitrite with deoxyhemoglobin: the effect of nitrite concentration and diphosphoglycerate. Biochemistry 46:11650-9
Nagababu, Enika; Rifkind, Joseph M (2007) Measurement of plasma nitrite by chemiluminescence without interference of S-, N-nitroso and nitrated species. Free Radic Biol Med 42:1146-54
Nagababu, Enika; Ramasamy, Somasundaram; Rifkind, Joseph M (2006) S-nitrosohemoglobin: a mechanism for its formation in conjunction with nitrite reduction by deoxyhemoglobin. Nitric Oxide 15:20-9
Lee, Garrick D; Longo, Dan L; Wang, Yue et al. (2006) Transient improvement in cognitive function and synaptic plasticity in rats following cancer chemotherapy. Clin Cancer Res 12:198-205
Rifkind, Joseph M; Nagababu, Enika; Ramasamy, Somasundaram (2006) Nitric oxide redox reactions and red cell biology. Antioxid Redox Signal 8:1193-203
Ravi, Luke B; Poosala, Suresh; Ahn, Dongchoon et al. (2005) Red cell interactions with amyloid-beta(1-40) fibrils in a murine model. Neurobiol Dis 19:28-37
Venkatesh, Balan; Venkatesh, S; Jayadevan, S et al. (2005) Studies on heme release from normal and metal ion reconstituted hemoglobin mediated through ionic surfactant. Biopolymers 80:18-25
Martinez, Alfredo; Oh, Hae-Ryong; Unsworth, Edward J et al. (2004) Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator. Biochem J 383:413-8
Jia, Yiping; Ramasamy, Somasundaram; Wood, Francine et al. (2004) Cross-linking with O-raffinose lowers oxygen affinity and stabilizes haemoglobin in a non-cooperative T-state conformation. Biochem J 384:367-75

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