Disease relevance of Ahsg

• An osteoblast-like cell line (UMR 106-01 BSP), cloned from a transplantable osteosarcoma, was cultured in the presence of parathyroid hormone (PTH1-34) and metabolically labeled with [35S]sulfate, [3H]glucosamine, and [3H]tyrosine to determine proteoglycan, glycoconjugate, and protein synthesis, respectively [1].
• The possible effect of EPO treatment in the ethinyl-estradiol (EE) induced cholestasis in the rat was investigated by measuring the hepatic transport of sulfobromophthalein (BSP) (plasma clearance and biliary secretion) and bile flow [2].
• Thus, respiratory depression with hypoxia may contribute to morphine-induced effects on BSP disposition, but altered blood gases cannot account fully for these narcotic effects [3].
• Hypercapnia and acidosis alone did not affect BSP disposition, while hypoxia without hypercapnia decreased its plasma clearance to 5.5 +/- 0.3 ml X min-1 and increased liver levels to 339.1 +/- 35.1 micrograms X g-1 [3].
• Since narcotics depress respiration, effects of hypoxia, hypercapnia, and acidosis on BSP disposition were studied [3].

High impact information on Ahsg

• The rat protein encoded by clone pp63 is a fetuin/alpha 2-HS glycoprotein-like molecule, but is it the tyrosine kinase inhibitor pp63 [4]?
• Previous studies in cultured rat hepatocytes revealed that initial uptake of sulfobromophthalein (BSP) was markedly reduced upon removal of Cl- from the medium [5].
• Affinity of BSP for albumin was Cl(-)-independent, and was approximately 10% of its affinity for cells in the presence of Cl-. These results indicate that extracellular Cl- modulates the affinity of BSP for its hepatocyte transporter [5].
• This expressed chloride-dependent BSP uptake system exhibited saturation kinetics (apparent Km approximately 6.2 microM) and efficiently extracted BSP from its binding sites on BSA [6].
• Size fractionation of total rat liver mRNA revealed that a 2.0- to 3.5-kb size-class mRNA was sufficient to express the hepatic chloride-dependent BSP uptake system [6].

Chemical compound and disease context of Ahsg

• Similar hypoxia and hypercapnia caused by breathing 9% O2 and 8% CO2 in the absence of morphine caused plasma BSP clearance to be decreased to 4.4 +/- 0.2 ml X min-1 and 40-min hepatic BSP to be increased to 292.5 +/- 31.8 micrograms X g-1 [3].
• Male urethane-anesthetized Wistar rats with biliary fistulas were infused for 60 min i.v. with sulfobromophthalein (BSP) or BSP-glutathione conjugate (BSP-GSH) at 594 nmol/100 g/min [7].
• Methotrexate entry into H35 hepatoma cells is mediated by the transport system which is shared by folate coenzymes and is not inhibited by cholic acid, BSP or sulfhydryl reagents [8].
• Another iv combination dose (25 mg BSP/kg body weight, followed by 15 mg antipyrine/kg 0.5 hr later) and a dose of 15 mg antipyrine/kg body weight only was administered to rats pretreated with phenobarbital (90 mg/kg body weight) for 6 days [9].
• This study investigated the feasibility of using concurrent iv administration of antipyrine (15 mg/kg body weight) and bromosulphophthalein (BSP; 25 mg/kg) in the rat [9].

Biological context of Ahsg

• A complementary DNA (cDNA) for the 59 kD bone sialoprotein, which is supposed to be the rat counterpart of human alpha 2-HS glycoprotein (alpha 2-HSG) and is synthesized by both hepatocytes and osteoblasts, has been cloned from a rat liver cDNA library [10].
• Hence, the LPM-BSP/bilirubin binding protein plays a role in the carrier-mediated uptake of BSP and bilirubin by hepatocytes [11].
• EE decreased the secretory rate maximum (SRM) of tauroursodeoxycholate, (-71%) and bromosulfophthalein (BSP; -60%), as well as the expression of the BSP canalicular carrier, mrp2; SIL failed to increase mrp2 expression, and had only a marginal beneficial effect on both tauroursodeoxycholate and BSP SRM values [12].
• We have determined the amino acid sequence of rat bone sialoprotein (BSP) [13].
• We have previously observed that the Ya subunit-containing glutathione (GSH) S-transferases from rat liver exhibit a common high affinity binding site for lithocholic acid, bilirubin, and sulfobromophthalein (BSP) (1984. J. Lipid Res. 25: 1177-1183) [14].

Anatomical context of Ahsg

• Injection of oocytes with rat liver poly(A)+RNA resulted in the functional expression of chloride-dependent sulfobromophthalein (BSP) uptake within 3-5 d [6].
• To investigate the relative role of the first two of them in accounting for the hepatic uptake of organic anions, we measured the initial rates of uptake of 35S-labeled BSP into rat liver plasma-membrane vesicles [15].
• Gel chromatography of NAR liver cytosol with BSP revealed three BSP peaks, fractions X, Y, and Z; fraction X was the major component of BSP binding [16].
• In vivo implant assays demonstrated implant mineralization accompanied by vascularization and the presence of the bone matrix proteins, BSP and BAG-75 [17].
• We conclude that the uncoupling of biliary lipids from bile-salt secretion by BSP occurs at the level of the bile canaliculus following the secretion of unconjugated BSP [18].

Associations of Ahsg with chemical compounds

• To clarify sulfobromophthalein (BSP) and bilirubin uptake mechanisms, isolated rat hepatocytes were incubated with [35S]BSP [11].
• Intravenously administered BSP (5 mumol/kg) rapidly appeared in bile as the free form and the glutathione conjugate in normal rats and NAR; 41% and 57% of injected BSP was excreted within 60 min in NAR and control rat bile, respectively [16].
• Phenobarbital treatment increased the electrogenic transport of [35S]sulfobromophthalein (BSP) (5 and 50 microM) but not the electrogenic uptake of [14C] glycocholic acid (10 and 200 microM) [19].
• The inhibition by S-butylglutathione, the GSH analogue ophthalmic acid, and by BSP was competitive in nature, although BSP also produced a slight decrease in Vmax, suggesting a mixed type of inhibition [20].
• Avidin affinity purification of bone extract labeled with biotinylated primary amine in the presence of tTG, in conjunction with Western blotting, permitted identification of three major noncollagenous TG substrates in bone: osteopontin (OPN), bone sialoprotein (BSP), and alpha2 HS-glycoprotein (AHSG), of which the latter two are novel substrates [21].

Analytical, diagnostic and therapeutic context of Ahsg

• Liver perfusion with exogenous BSP-glutathione provided results similar to those obtained with BSP [22].
• Hepatocytes contributing to the uptake, metabolism and biliary secretion of BSP were directly assessed qualitatively by light microscopy, and also semiquantitatively by microspectrophotometry [22].
• A simultaneous intravenous infusion of sulfobromophthalein (BSP) (0.3 mg.min-1.100 g-1) and ursodeoxycholate (UDC) or tauroursodeoxycholate (TUDC) (1.2 mumol.min-1.100 g-1) caused a significantly higher excretion rate of BSP than in the control value without bile salt infusion [23].
• To investigate the role of sex steroids in the sex-related difference in the hepatic uptake of organic anions, sulphobromophthalein (bromsulphalein, BSP) transport was measured in hepatocytes isolated from rats either deprived of hormonal influence by castration at prepubertal age or after hormonal substitution [24].
• METHODS: Sulfobromophthalein uptake was measured by rapid filtration in isolated hepatocytes without albumin (up to 13 microM sulfobromophthalein) and with 600 microM albumin (sulfobromophthalein:albumin from 0.03:1 to 1:1), a physiologic setting which greatly reduces the unbound BSP concentration [25].

References