UGT1A1 dysfunction increases liver burden and aggravates hepatocyte damage caused by long-term bilirubin metabolism disorder.

Biochemical Pharmacology
Dan LiuZhongqiu Liu

Abstract

UGT1A1 is the only enzyme that can metabolize bilirubin, and its encoding gene is frequently mutated. UGT1A1*6 (G71R) is a common mutant in Asia which leads to the decrease of UGT1A1 activity and abnormal bilirubin metabolism. However, it is not clear whether low UGT1A1 activity-induced bilirubin metabolism disorder increases hepatocyte fragility. ugt1a+/- mice were used to simulate the UGT1A1*6 (G71R) population. Under the same CCl4 induction condition, ugt1a+/- mice showed severer liver damage and fibrosis, indicating that ugt1a1 dysfunction increased liver burden and aggravated hepatocyte damage. In the animal experiment with a continuous intraperitoneal injection of bilirubin, the ugt1a+/- mice livers had more serious unconjugated bilirubin accumulation. The accumulated bilirubin leads to hyperphosphorylation of IκB-α, Ikk-β, and p65 and a significant increase of inflammatory factor. The α-SMA and Collagen I proteins markedly up-regulated in the ugt1a+/- mice livers. Immunofluorescence and confocal microscopy showed that hepatic stellate cells and Kupffer cells were activated in ugt1a+/- mice. Comprehensive results show that there was a crosstalk relationship between low UGT1A1 activity-bilirubin-liver damage. Furthermore, ...Continue Reading

References

Jul 20, 2002·Molecular Pharmacology·John M SeubertJohn R Bend
Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Tom Luedde, Robert F Schwabe
Apr 29, 2011·Journal of Ethnopharmacology·Chunna YuSu Zeng
Aug 13, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·Monika Bhadauria
Mar 16, 2013·World Journal of Gastrointestinal Pharmacology and Therapeutics·Binita Shah, Gaurang Shah
Jun 9, 2015·Biochemical and Biophysical Research Communications·Ying Hui LiEun-Hee Cho
Mar 5, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xi LiHuichang Bi
Mar 12, 2017·Molecular Pharmacology·Mei-Fei YuehRobert H Tukey
Mar 18, 2017·Molecular Immunology·Peizhi LiJianping Gong
Mar 21, 2017·Neuropharmacology·Cesare Mancuso
Mar 24, 2017·Journal of Natural Products·Ye LiuHan-Li Ruan
Jun 16, 2017·Cell Death & Disease·Hongbiao HuangJinbao Liu
Aug 15, 2017·Toxicology Mechanisms and Methods·Panhong GouBenzhong Zhang
Oct 27, 2017·European Journal of Pharmacology·Xi LiHuichang Bi
Mar 2, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lauren WeaverTerry D Hinds
Jun 23, 2018·Asia-Pacific Journal of Clinical Oncology·Yuwei YangFen Huang
Aug 15, 2018·Cancer Chemotherapy and Pharmacology·Hisham QosaDonna A Volpe
Sep 14, 2018·Scientific Reports·Eleonora VianelloSilvia Gazzin
Apr 10, 2019·International Journal of Molecular Sciences·Jacopo BaglieriTatiana Kisseleva
Aug 24, 2019·Nature Reviews. Gastroenterology & Hepatology·Ju Dong YangLewis R Roberts
Nov 5, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Dan LiuCai Yan Wang
Feb 6, 2020·Medicinal Research Reviews·Libor Vítek
Feb 6, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Tingting LiQinghua Hu
Apr 8, 2020·Oxidative Medicine and Cellular Longevity·M I NasserPing Zhu

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.