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Role of Rh (rhesus) complex in K‐Cl cotransport (KCC) regulation in red blood cells (RBCs) of Rh and Rh‐associated glycoprotein (RhAg) knockout (KO) mice
Author(s) -
Lauf Peter K.,
Adragorma C.,
Goossens Dominique,
Cartron JeanPierre
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.797.5
Subject(s) - cotransporter , chemistry , microbiology and biotechnology , n ethylmaleimide , medicine , endocrinology , biochemistry , sodium , biology , organic chemistry
The Rh blood group is a macromolecular complex of protein subunits (D and CE), RhAG, a NH 3 /CO 2 gas transporter (PNAS 101:17222,2004; FASEB J 22;1,2008), and accessory proteins (ICAM‐4/LW, CD47 and GPB). In the mild hemolytic human Rh null disorder, the Rh complex is absent/severely deficient. Altered K fluxes have been found in Rh null RBC (Blood 48: 457, 1976). A double blind study on male (m) or female (f) wild type (WT), and Rh −/− and Rhag −/− KO mice (Transf Clin Biol 13:164,2006) studied: Total, ouabain (O)‐sensitive Na/K pump, O‐insensitive+bumetanide (B)‐sensitive Na‐K‐2Cl cotransport (NKCC), and O‐ and B‐insensitive KCC ± the thiol alkylant N‐ethylmaleimide (NEM), staurosporine (STP, a kinase inhibitor) and Mg removal by A23187. Results 1) Total, Na/K pump, NKCC and basal KCC influx were not different between groups. 2) NEM activated KCC by >100 % (p<0.001) in both m/f Rh −/− and RhAg −/− , compared to WT. KCC activation by both STP, and Mg depletion (except for m Rh −/− ), was similar in m Rh −/− , m/f Rhag −/− RBCs and WT. Conclusion Thiol modification reveals a Rh‐complex role in KCC regulation, i.e. via protein phosphorylation or protein/protein interactions. However, unlike in human Rh null RBCs, Na/K pump and passive K‐"leak" fluxes were normal, an apparent difference in the Rh complex‐K transport association between mice and man. Support in part by a WSU School of Medicine Grant.