title: Role of membrane sialic acid and glycophorin protein in thorium induced aggregation and hemolysis of human erythrocytes.
abstract: Thorium-232 ((232)Th), a natural radionuclide from the actinide family, is abundantly present in monazite and other ores. It is used as one of the prime fuel materials in nuclear industry and may pose an exposure risk to nuclear workers and members of the public. Human erythrocytes, as a classical cellular membrane model, were coincubated with (232)Th in order to elucidate whether this naturally occurring important radionuclide produced perturbations to cell membrane. Present study revealed that erythrocytes underwent aggregation or lysis depending on the ratio of (232)Th to cell. Scanning electron micrographs showed that erythrocytes transformed into equinocytes and/or spherocytes after (232)Th treatment. Further examination of erythrocyte by atomic force microscopy suggested significant increase in surface roughness after (232)Th treatment. Experiments on neuraminidase treated and/or anti-GpA antibody blocked erythrocytes suggested significant role of membrane sialic acid and glycophorin A (GpA) protein in aggregation or hemolytic effects of (232)Th. Further results showed that (232)Th caused hemolysis by colloid osmotic mechanism, as evidenced by potassium efflux, osmotic protection and osmotic fragility studies. Osmoprotection experiments indicated that hemolysis get elicited through the formation of membrane pores of approximately 2.0 nm in size. Hemolysis studies in presence of inhibitors (TEA, bumetanide, DIDS and amiloride) revealed the role of K(+) channel, Na(+)/K(+)/2Cl(-) channel, Cl(-)/HCO(3)(-) anion exchanger and Na(+)/H(+) antiporter in (232)Th induced erythrolysis. Presence of non-diffusible cation (N-methyl d-glucasamine) or anion (gluconate) in erythrocyte suspending medium further confirm the role of Na(+) and Cl(-) influx in hemolytic effect of (232)Th. These findings provide significant insight in structural, biochemical and osmotic toxic effects of (232)Th on human erythrocytes.
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Center, Mumbai 400 085, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Manjoor
authors.initials: M
authors.lastname: Ali
authors.forename: Badri N
authors.initials: BN
authors.lastname: Pandey
authors.forename: Puthusserickal A
authors.initials: PA
authors.lastname: Hassan
authors.forename: Kaushala P
authors.initials: KP
authors.lastname: Mishra
mesh_terms: D000328:Adult; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004903:Erythrocyte Aggregation / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006021:Glycophorins / Q000737:chemistry / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009995:Osmosis / Q000187:drug effects; D009996:Osmotic Fragility / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D013910:Thorium / Q000633:toxicity*
chemical_list: D006021:Glycophorins; D013910:Thorium; D019158:N-Acetylneuraminic Acid; D011188:Potassium