• Je něco špatně v tomto záznamu ?

Effects of Heme Site (FA1) Ligands Bilirubin, Biliverdin, Hemin, and Methyl Orange on the Albumin Binding of Site I Marker Warfarin: Complex Allosteric Interactions

B. Lemli, Z. Lomozová, T. Huber, A. Lukács, M. Poór

. 2022 ; 23 (22) : . [pub] 20221113

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22032673

Human serum albumin (HSA) is the most abundant plasma protein in circulation. The three most important drug-binding sites on HSA are Sudlow's Site I (subdomain IIA), Sudlow's Site II (subdomain IIIA), and Heme site (subdomain IB). Heme site and Site I are allosterically coupled; therefore, their ligands may be able to allosterically modulate the binding affinity of each other. In this study, the effects of four Heme site ligands (bilirubin, biliverdin, hemin, and methyl orange) on the interaction of the Site I ligand warfarin with HSA were tested, employing fluorescence spectroscopic, ultrafiltration, and ultracentrifugation studies. Our major results/conclusions are the following. (1) Quenching studies indicated no relevant interaction, while the other fluorescent model used suggested that each Heme site ligand strongly decreases the albumin binding of warfarin. (2) Ultrafiltration and ultracentrifugation studies demonstrated the complex modulation of warfarin-HSA interaction by the different Heme site markers; for example, bilirubin strongly decreased while methyl orange considerably increased the bound fraction of warfarin. (3) Fluorescence spectroscopic studies showed misleading results in these diligand-albumin interactions. (4) Different Heme site ligands can increase or decrease the albumin binding of warfarin and the outcome can even be concentration dependent (e.g., biliverdin and hemin).

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22032673
003      
CZ-PrNML
005      
20230131150734.0
007      
ta
008      
230120s2022 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/ijms232214007 $2 doi
035    __
$a (PubMed)36430492
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Lemli, Beáta $u Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary $u Green Chemistry Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary $1 https://orcid.org/0000000189031337
245    10
$a Effects of Heme Site (FA1) Ligands Bilirubin, Biliverdin, Hemin, and Methyl Orange on the Albumin Binding of Site I Marker Warfarin: Complex Allosteric Interactions / $c B. Lemli, Z. Lomozová, T. Huber, A. Lukács, M. Poór
520    9_
$a Human serum albumin (HSA) is the most abundant plasma protein in circulation. The three most important drug-binding sites on HSA are Sudlow's Site I (subdomain IIA), Sudlow's Site II (subdomain IIIA), and Heme site (subdomain IB). Heme site and Site I are allosterically coupled; therefore, their ligands may be able to allosterically modulate the binding affinity of each other. In this study, the effects of four Heme site ligands (bilirubin, biliverdin, hemin, and methyl orange) on the interaction of the Site I ligand warfarin with HSA were tested, employing fluorescence spectroscopic, ultrafiltration, and ultracentrifugation studies. Our major results/conclusions are the following. (1) Quenching studies indicated no relevant interaction, while the other fluorescent model used suggested that each Heme site ligand strongly decreases the albumin binding of warfarin. (2) Ultrafiltration and ultracentrifugation studies demonstrated the complex modulation of warfarin-HSA interaction by the different Heme site markers; for example, bilirubin strongly decreased while methyl orange considerably increased the bound fraction of warfarin. (3) Fluorescence spectroscopic studies showed misleading results in these diligand-albumin interactions. (4) Different Heme site ligands can increase or decrease the albumin binding of warfarin and the outcome can even be concentration dependent (e.g., biliverdin and hemin).
650    _2
$a lidé $7 D006801
650    12
$a biliverdin $7 D001664
650    12
$a warfarin $x farmakologie $7 D014859
650    _2
$a hem $x metabolismus $7 D006418
650    _2
$a hemin $7 D006427
650    _2
$a bilirubin $7 D001663
650    _2
$a ligandy $7 D008024
650    _2
$a sérový albumin $x metabolismus $7 D012709
655    _2
$a časopisecké články $7 D016428
700    1_
$a Lomozová, Zuzana $u The Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000192057714
700    1_
$a Huber, Tamás $u Department of Biophysics, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
700    1_
$a Lukács, András $u Department of Biophysics, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
700    1_
$a Poór, Miklós $u Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary $u Lab-on-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary $1 https://orcid.org/0000000314257459
773    0_
$w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 23, č. 22 (2022)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36430492 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230120 $b ABA008
991    __
$a 20230131150730 $b ABA008
999    __
$a ok $b bmc $g 1891430 $s 1184008
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2022 $b 23 $c 22 $e 20221113 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
LZP    __
$a Pubmed-20230120

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...