Identification of high density lipoprotein-binding proteins, including a glycosyl phosphatidylinositol-anchored membrane dipeptidase, in rat lung and type II pneumocytes.
Numerous communications have indicated that specific binding proteins for high density lipoprotein (HDL) exist in addition to the well characterized candidate HDL receptor SR-BI, but structural information was presented only in a few cases, and most of the work was aimed at the liver and steroidogenic glands. In this study, we purified two HDL-binding proteins by standard procedures from rat lung tissue. One of these membrane glycoproteins was identified by N-terminal sequencing and with specific antibodies as HB2, a previously described HDL-binding protein, whereas the other one was identified as a glycosyl phosphatidylinositol-anchored membrane dipeptidase (MDP). The apparent dissociation constant of the HDL binding was determined by solid phase assay to be 2.1 microg/ml (HB2) and 25 microg/ml (MDP). MDP also exerts affinity to low density lipoprotein (LDL) on ligand blots, and competition between HDL and LDL was observed, but analysis by solid phase assay showed that very high concentrations of LDL are required. The physiologic relevance of this effect is therefore questionable. The level in type II pneumocyte membranes of both binding proteins, MDP and HB2, increased when the plasma lipoprotein concentration was reduced by treatment of rats with 4-aminopyrazolo[3,4-d]-pyrimidine, consistent with a function to facilitate lipid uptake in vivo. The binding proteins were also dramatically upregulated by feeding rats a vitamin E-depleted diet. Vitamin E uptake requires interaction between HDL and type II cells, suggesting a role of HB2 and MDP also in this process.
Witt
W
W
Department of Medicine, Humboldt University, Berlin, Germany.
Kolleck
I
I
Rüstow
B
B
D000595:Amino Acid Sequence; D000818:Animals; D008076:Cholesterol, HDL / Q000032:analysis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004032:Diet; D004150:Dipeptidases / Q000378:metabolism*; D004586:Electrophoresis; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D037102:Lectins; D008168:Lung / Q000166:cytology* / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D014811:Vitamin E Deficiency / Q000378:metabolism
D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D017261:Glycosylphosphatidylinositols; C087410:Hdlbp protein, rat; D037102:Lectins; D008565:Membrane Proteins; D004150:Dipeptidases; C038937:dipeptidase