- Email: [email protected]
F146. Magnetization transfer characterization of red cells from patients with unstable hemoglobin disease
Vol. 32, Nos. 2-3
Free Communications
303
damage of erythrocytes accompanied with spectrin crosslinking disturbs the flow of erythrocytes in blood vessels and FREE COMMUNICATIONS BIORHEOLOGY
146-150:
MOLECULAR
F146. MAGNETIZATION TRANSFER CHARACTERIZATION OF RED CELLS FROM PATIENTS WITH UNSTABLE HEMOGLOBIN DISEASE N. UYESAKA, M. S O G A M I t , S. ERA++, K. K A T O * S. HASEGAWA, K. USUKI*, T. O O N I S H I * , AND A. N. S C H E C H T E R * * Department of Physiology, Nippon Medical School, Tokyo, Japan tDivision of Medical Sciences, Fujita Health University, Tokyo, Japan SDepartment of Physiology, School of Medical, Gifu University, Gifu, Japan *The Kanto Teishin Hospital, Tokyo, Japan **Laboratory of Chemical Biology, NIDDK, NIH, Bethesda, MD, USA We measured intermolecular cross-relaxation times (TIs) from irradiated macromolecular protons to observed water protons and spin-lattice relaxation times (TI) of water protons in red blood cells (RBC) from patients with unstable hemoglobin (HB) disease (HB K61n and HB Yokohama) and RBC treated with phenylhydrazine. Phenylhydrazine-treated RBC showed dispersed formation of small Heinz bodies and impaired filterability through nickel mesh in a dose-dependent manner. RBC from a patient with HB Yokohama presented many large and often solitary Heinz bodies and strongly impaired filterability, while RBC from a patient with HB K61n, who does not undergo splenectomy, showed few microscopically typical Heinz bodies and virtually normal filterability. RBC from the patients, even in HB K61n disease, exhibited a more marked shortening of TIS than phenylhydrazine-treated RBC. Conventional TI measurements were not sensitive to these differences. Since TIS values are prinlarily determined by the efficiency of spin diffusion and the shortening of T m occurred prior to a high yield of typical Heinz bodyformation, it is likely that these unstable HB molecules themselves have strong inter-residue interactions and lead to eventual restricted motion of HB molecules, thereby suggesting that the oxidant-treated RBC are not a suitable model for studying tile molecular pathophysiology of unstable HB disease. We conclude that TIS measurements are very sensitive for the detection of conformational changes of HB molecules and resultant association of HB molecules within RBC and may be useful for studying other diseases due to HB-membrane association, such as the thalassemia syndromes, or reversible association within the RBC, as in sickle cell disease, in cells ex vivo.
Free Communications
303
damage of erythrocytes accompanied with spectrin crosslinking disturbs the flow of erythrocytes in blood vessels and FREE COMMUNICATIONS BIORHEOLOGY
146-150:
MOLECULAR
F146. MAGNETIZATION TRANSFER CHARACTERIZATION OF RED CELLS FROM PATIENTS WITH UNSTABLE HEMOGLOBIN DISEASE N. UYESAKA, M. S O G A M I t , S. ERA++, K. K A T O * S. HASEGAWA, K. USUKI*, T. O O N I S H I * , AND A. N. S C H E C H T E R * * Department of Physiology, Nippon Medical School, Tokyo, Japan tDivision of Medical Sciences, Fujita Health University, Tokyo, Japan SDepartment of Physiology, School of Medical, Gifu University, Gifu, Japan *The Kanto Teishin Hospital, Tokyo, Japan **Laboratory of Chemical Biology, NIDDK, NIH, Bethesda, MD, USA We measured intermolecular cross-relaxation times (TIs) from irradiated macromolecular protons to observed water protons and spin-lattice relaxation times (TI) of water protons in red blood cells (RBC) from patients with unstable hemoglobin (HB) disease (HB K61n and HB Yokohama) and RBC treated with phenylhydrazine. Phenylhydrazine-treated RBC showed dispersed formation of small Heinz bodies and impaired filterability through nickel mesh in a dose-dependent manner. RBC from a patient with HB Yokohama presented many large and often solitary Heinz bodies and strongly impaired filterability, while RBC from a patient with HB K61n, who does not undergo splenectomy, showed few microscopically typical Heinz bodies and virtually normal filterability. RBC from the patients, even in HB K61n disease, exhibited a more marked shortening of TIS than phenylhydrazine-treated RBC. Conventional TI measurements were not sensitive to these differences. Since TIS values are prinlarily determined by the efficiency of spin diffusion and the shortening of T m occurred prior to a high yield of typical Heinz bodyformation, it is likely that these unstable HB molecules themselves have strong inter-residue interactions and lead to eventual restricted motion of HB molecules, thereby suggesting that the oxidant-treated RBC are not a suitable model for studying tile molecular pathophysiology of unstable HB disease. We conclude that TIS measurements are very sensitive for the detection of conformational changes of HB molecules and resultant association of HB molecules within RBC and may be useful for studying other diseases due to HB-membrane association, such as the thalassemia syndromes, or reversible association within the RBC, as in sickle cell disease, in cells ex vivo.