TITLE: STUDY OF THE EFFECTS OF NITRIC OXIDE ON SICKLE CELL DISEASE

SPEAKER: Xuili Xu

TIME: Monday May 3, 2004 at 1:30 PM

PLACE: George P. Williams, Jr. Lecture Hall, (Olin 101)

Sickle cell disease (SCD) is a serious vascular disorder. The disease is caused by a single point mutation within hemoglobin (Hb), which causes polymerization of Hb, leading to abnormally-shaped and rigid red cells that cause obstruction of small blood vessels and decreased oxygen-carrying capacity. Inhalation of nitric oxide (NO) in acceptable amounts has been tried as a treatment of SCD, based on the vaso-dilating function of NO. In human circulation, NO initiates reactions that result in relaxation of smooth muscle. This research focuses on the biophysical aspects of NO therapy for patients with SCD. We examined the solubilizing effect, the ability to reduce polymerization, of partially NO-ligated sickle Hb and the ability of NO to undergo the intramolecular transfer. Our results showed that NO therapy doesn't benefit patients through solubilizing effect and no evidence for intramolecular transfer of NO was found. Contaminating nitrite could play a key role in previous reports of intramolecular transfer due to the reaction between Hb and nitrite producing NO. Simulations of the diffusion of NO produced by this reaction within erythrocytes showed that the amount of NO diffusing out is not high enough to function as a vaso-dilator. An intermediate species in this reaction might play an important role in the delivery and preservation of biological activity of NO in the human body.