organic solute transporter
Recently Published Documents


TOTAL DOCUMENTS

50
(FIVE YEARS 11)

H-INDEX

17
(FIVE YEARS 2)

2021 ◽  
pp. MOLPHARM-AR-2021-000345
Author(s):  
William Alan Murphy ◽  
James John Beaudoin ◽  
Tuomo Laitinen ◽  
Noora Sjöstedt ◽  
Melina M Malinen ◽  
...  

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Paul A. Dawson

The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [2, 5, 1]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to steroid movement [6]. Bile acid transport is suggested to be facilitative and independent of sodium, potassium, chloride ions or protons [5, 2]. OSTα/OSTβ heterodimers have been shown to transport [3H]taurocholic acid, [3H]dehydroepiandrosterone sulphate, [3H]estrone-3-sulphate, [3H]pregnenolone sulphate and [3H]dehydroepiandrosterone sulphate [2, 5, 6]. OSTα/OSTβ-mediated transport of bile salts is inhibited by clofazimine [10]. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM 'ancillary' protein, both of which are thought to have intracellular C-termini [8]. Both proteins function in solute transport [8, 4]. Inherited mutations in OSTα and OSTβ are associated with liver disease and congenital diarrhea in children [9, 7].


2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Paul A. Dawson

The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [2, 4, 1]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to steroid movement [5]. Bile acid transport is suggested to be facilitative and independent of sodium, potassium, chloride ions or protons [4, 2]. OSTα/OSTβ heterodimers have been shown to transport [3H]taurocholic acid, [3H]dehydroepiandrosterone sulphate, [3H]estrone-3-sulphate, [3H]pregnenolone sulphate and [3H]dehydroepiandrosterone sulphate [2, 4, 5]. OSTα/OSTβ-mediated transport of bile salts is inhibited by clofazimine [9]. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM 'ancillary' protein, both of which are thought to have intracellular C-termini [7]. Both proteins function in solute transport [7, 3]. Inherited mutations in OSTα and OSTβ are associated liver disease and congenital diarrhea in children [8, 6].


Hepatology ◽  
2020 ◽  
Vol 71 (5) ◽  
pp. 1879-1882 ◽  
Author(s):  
Emily Gao ◽  
Huma Cheema ◽  
Nadia Waheed ◽  
Iqra Mushtaq ◽  
Nihan Erden ◽  
...  

2020 ◽  
Vol 176 (1) ◽  
pp. 34-45 ◽  
Author(s):  
James J Beaudoin ◽  
Jacqueline Bezençon ◽  
Noora Sjöstedt ◽  
John K Fallon ◽  
Kim L R Brouwer

Abstract Organic solute transporter (OST) α/β is a key bile acid transporter expressed in various organs, including the liver under cholestatic conditions. However, little is known about the involvement of OSTα/β in bile acid-mediated drug-induced liver injury (DILI), a major safety concern in drug development. This study investigated whether OSTα/β preferentially transports more hepatotoxic, conjugated, primary bile acids and to what extent xenobiotics inhibit this transport. Kinetic studies with OSTα/β-overexpressing cells revealed that OSTα/β preferentially transported bile acids in the following order: taurochenodeoxycholate > glycochenodeoxycholate > taurocholate > glycocholate. The apparent half-maximal inhibitory concentrations for OSTα/β-mediated bile acid (5 µM) transport inhibition by fidaxomicin, troglitazone sulfate, and ethinyl estradiol were: 210, 334, and 1050 µM, respectively, for taurochenodeoxycholate; 97.6, 333, and 337 µM, respectively, for glycochenodeoxycholate; 140, 265, and 527 µM, respectively, for taurocholate; 59.8, 102, and 117 µM, respectively, for glycocholate. The potential role of OSTα/β in hepatocellular glycine-conjugated bile acid accumulation and cholestatic DILI was evaluated using sandwich-cultured human hepatocytes (SCHH). Treatment of SCHH with the farnesoid X receptor agonist chenodeoxycholate (100 µM) resulted in substantial OSTα/β induction, among other proteomic alterations, reducing glycochenodeoxycholate and glycocholate accumulation in cells+bile 4.0- and 4.5-fold, respectively. Treatment of SCHH with troglitazone and fidaxomicin together under cholestatic conditions resulted in increased hepatocellular toxicity compared with either compound alone, suggesting that OSTα/β inhibition may accentuate DILI. In conclusion, this study provides insights into the role of OSTα/β in preferential disposition of bile acids associated with hepatotoxicity, the impact of xenobiotics on OSTα/β-mediated bile acid transport, and the role of this transporter in SCHH and cholestatic DILI.


2020 ◽  
Vol 97 (4) ◽  
pp. 259-266 ◽  
Author(s):  
Ying Zhou ◽  
Chaonan Ye ◽  
Yan Lou ◽  
Junqing Liu ◽  
Sheng Ye ◽  
...  

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Paul A. Dawson

The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [1, 3]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to steroid movement [4]. Bile acid transport is suggested to be facilitative and independent of sodium, potassium, chloride ions or protons [3, 1]. OSTα/OSTβ heterodimers have been shown to transport [3H]taurocholic acid, [3H]dehydroepiandrosterone sulphate, [3H]estrone-3-sulphate, [3H]pregnenolone sulphate and [3H]dehydroepiandrosterone sulphate [1, 3, 4]. OSTα/OSTβ-mediated transport of bile salts is inhibited by clofazimine [7]. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM 'ancillary' protein, both of which are thought to have intracellular C-termini [5]. Both proteins function in solute transport and bimolecular fluorescence complementation studies suggest the possibility of OSTα homo-oligomers, as well as OSTα/OSTβ hetero-oligomers [5, 2]. An inherited mutation in OSTβ is associated with congenital diarrhea in children [6].


Sign in / Sign up

Export Citation Format

Share Document