Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Cell Biol Int ; 48(5): 638-646, 2024 May.
Article in English | MEDLINE | ID: mdl-38328902

ABSTRACT

The bile salt export pump (ABCB11/BSEP) is a hepatocyte plasma membrane-resident protein translocating bile salts into bile canaliculi. The sequence alignment of the four full-length transporters of the ABCB subfamily (ABCB1, ABCB4, ABCB5 and ABCB11) indicates that the NBD-NBD contact interface of ABCB11 differs from that of other members in only four residues. Notably, these are all located in the noncanonical nucleotide binding site 1 (NBS1). Substitution of all four deviant residues with canonical ones (quadruple mutant) significantly decreased the transport activity of the protein. In this study, we mutated two deviant residues in the signature sequence to generate a double mutant (R1221G/E1223Q). Furthermore, a triple mutant (E502S/R1221G/E1223Q) was generated, in which the deviant residues of the signature sequence and Q-loop were mutated concurrently to canonical residues. The double and triple mutants showed 80% and 60%, respectively, of the activity of wild-type BSEP. As expected, an increasing number of mutations gradually impair transport as an intricate network of interactions within the ABC proteins ensures proper functioning.


Subject(s)
ATP-Binding Cassette Transporters , Nucleotides , ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 11/metabolism , Nucleotides/metabolism , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Mutation/genetics , Binding Sites
2.
Cell Biochem Biophys ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38332450

ABSTRACT

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease characterized by biliary infiltration, hepatic fibrosis and bile duct destruction. To date, treatment options for PSC are very limited. Therefore, the current study is aimed to investigate the therapeutic potential of berberine (BBR) against PSC. The disease was induced by feeding the mice with 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC) for four weeks. The serum biochemistry and liver histology were analyzed. Furthermore, the expression of farnesoid X receptor (FXR) was also evaluated by real-time PCR. The results indicated that berberine prevents the progression of PSC by modulating the expression of FXR which ultimately regulates other genes (including Cyp7A1 and BSEP) thus maintaining bile acids homeostasis. Furthermore, the docking analysis showed that berberine interacts with the binding pocket of FXR to activate the protein thus acting as an FXR agonist. In conclusion, data indicate that berberine protects the liver from PSC-related injury. This effect might be due to the modulation of FXR activity.

3.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 208-212, 2022 Jul 31.
Article in English | MEDLINE | ID: mdl-36495494

ABSTRACT

Cholestasis is characterized by impaired bile flow which results in inflammation, cirrhosis, and ultimately liver failure. The current study is aimed to evaluate the anti-cholestatic effect of silymarin against α-naphthylisothiocyanate (ANIT) induced cholestasis. Mice were gavaged with various doses of silymarin or ursodeoxycholic acid (UDCA) for 19 days. Then they were challenged with α-naphthylisothiocyanate (ANIT) and after 48 hours the animals were sacrificed to obtain blood and liver sections. Serum levels of bilirubin, aspartate transaminase (AST), alanine transaminase (ALP), and liver histology were analyzed. mRNA expression of selected transporters (Bile salt export pump (BSEP) and sodium taurocholate cotransporting polypeptide (NTCP)) and proteins (farnesoid x receptor (FXR) and Cytochrome P450 Family 7 Subfamily A Member 1 (Cyp7a1)) involved in bile acids biosynthesis, excretion and uptake were also evaluated by quantitative PCR. The results indicated that the serum levels of bilirubin, AST, and ALP were significantly higher in a cholestatic model group as compared to an untreated control group. However, in silymarin groups, the serum level of these parameters is significantly lower than in a cholestatic model group. Liver histology also showed that silymarin prevents ANIT-induced hepatic injury. mRNA expression of FXR, BSEP, and NTCP was downregulated and expression of Cyp7a1 was upregulated in a cholestatic model group as compared to an untreated control group. However, in silymarin treatment groups, the expression of FXR, BSEP and NTCP was upregulated and the expression of Cyp7a1 was downregulated as compared to the cholestatic model group. In conclusion, silymarin could alleviate hepatic injury by modulating the expression of genes involved in bile acid homeostasis.


Subject(s)
Cholestasis , Silymarin , Mice , Animals , 1-Naphthylisothiocyanate/toxicity , 1-Naphthylisothiocyanate/metabolism , Bile Acids and Salts/metabolism , Silymarin/pharmacology , Cholestasis/chemically induced , Cholestasis/drug therapy , Cholestasis/genetics , Liver/metabolism , Aspartate Aminotransferases , RNA, Messenger/genetics , RNA, Messenger/metabolism
4.
Protein Pept Lett ; 25(2): 148-163, 2018.
Article in English | MEDLINE | ID: mdl-29359659

ABSTRACT

BACKGROUND: Increasing population and industrialization are continuously oppressing the existing energy resources and depleting the global fuel reservoirs. The elevated pollutions from the continuous consumption of non-renewable fossil fuels also seriously contaminating the surrounding environment. The use of alternate energy sources can be an environment-friendly solution to cope these challenges. Among the renewable energy sources biofuels (biomass-derived fuels) can serve as a better alternative to reduce the reliance on non-renewable fossil fuels. Bioethanol is one of the most widely consumed biofuels of today's world. OBJECTIVE: The main objective of this review is to highlight the significance of lignocellulosic biomass as a potential source for the production of biofuels like bioethanol, biodiesel or biogas. METHODS: We discuss the application of various methods for the bioconversion of lignocellulosic biomass to end products i.e. biofuels. The lignocellulosic biomass must be pretreated to disintegrate lignocellulosic complexes and to expose its chemical components for downstream processes. After pretreatment, the lignocellulosic biomass is then subjected to saccharification either via acidic or enzymatic hydrolysis. Thereafter, the monomeric sugars resulted from hydrolysis step are further processed into biofuel i.e. bioethanol, biodiesel or butanol etc. through the fermentation process. The fermented impure product is then purified through the distillation process to obtain pure biofuel. CONCLUSION: Renewable energy sources represent the potential fuel alternatives to overcome the global energy crises in a sustainable and eco-friendly manner. In future, biofuels may replenish the conventional non-renewable energy resources due to their renewability and several other advantages. Lignocellulosic biomass offers the most economical biomass to generate biofuels. However, extensive research is required for the commercial production of an efficient integrated biotransformation process for the production of lignocellulose mediated biofuels.


Subject(s)
Biofuels , Biomass , Biotechnology/methods , Lignin/chemistry , Catalysis , Fermentation , Hydrolysis , Lignin/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...