Article
Biochemistry & Molecular Biology
Isabelle M. Capell-Hattam, Nicole M. Fenton, Hudson W. Coates, Laura J. Sharpe, Andrew J. Brown
Summary: In this study, researchers identified the noncatalytic protein ERG28 as a player in mammalian cholesterol synthesis. They found that ERG28 is transcriptionally regulated by the transcription factor SREBP-2 and interacts with enzymes involved in cholesterol synthesis. Knockout of ERG28 resulted in reduced cholesterol levels and impaired cholesterol synthesis. Additionally, ERG28 knockout also affected the activation of SREBP-2 under sterol-replete conditions. These findings highlight the importance of ERG28 in cholesterol synthesis and suggest that further understanding of this protein could contribute to therapeutic strategies for diseases associated with aberrant cholesterol metabolism.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Branka Sosic-Jurjevic, Dieter Lutjohann, Svetlana Trifunovic, Sladan Pavlovic, Slavica Borkovic Mitic, Ljubisa Jovanovic, Natasa Ristic, Ljiljana Marina, Vladimir Ajdzanovic, Branko Filipovic
Summary: Age and sex have an impact on serum cholesterol levels, with more significant effects observed in aged females. Poorer hepato-intestinal health and increased jejunal cholesterol absorption are associated with the higher serum cholesterol levels in aged females. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Helene Johansson, Jonas Norskov Sondergaard, Carl Jorns, Claudia Kutter, Ewa C. S. Ellis
Summary: Bile acids (BAs) are essential for lipid absorption in the intestine, and their metabolism is tightly regulated by feedback mechanisms. FGF19 plays a crucial role in maintaining BA homeostasis, while CDCA can independently regulate BA synthesis by increasing FGF19 expression and subsequently reducing BA synthesis.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Luiza Borges Manna, Catherine Williamson
Summary: Normal pregnancy is associated with changes in metabolism in the third trimester, influenced by nuclear receptors such as FXR and LXR. Clock genes may also play a role in late pregnancy metabolic alterations. This can impact fetal growth and susceptibility to metabolic disorders like gestational diabetes mellitus and intrahepatic cholestasis of pregnancy.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Clavia Ruth Wooton-Kee
Summary: Copper is an essential trace element that is necessary for various cellular processes, but excess copper accumulation can be toxic. The liver plays a crucial role in maintaining copper homeostasis. Wilson's disease, an autosomal recessive disorder, is caused by mutations in the ATP7B gene and requires lifelong treatment or liver transplantation. Current treatment options focus on reducing copper levels and cellular toxicity. Studies have shown altered hepatic metabolism and impaired hepatic nuclear receptor activity in Wilson's disease patients.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Lillian Russo-Savage, Ira G. Schulman
Summary: Liver X receptors are ligand-dependent transcription factors that regulate transcription by directly binding cholesterol derivatives, playing important roles in lipid homeostasis throughout the body. In the liver, LXR controls cholesterol and fatty acid metabolism, and modifying LXR activity can influence the pathology of liver diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Lisa Goedtke, Heike Sprenger, Ute Hofmann, Felix F. Schmidt, Helen S. Hammer, Ulrich M. Zanger, Oliver Poetz, Albrecht Seidel, Albert Braeuning, Stefanie Hessel-Pras
Summary: PAHs are environmental pollutants generated by incomplete combustion of organic matter, which can induce their own metabolism by activating AHR and CAR. Most PAHs activate AHR, while non-carcinogenic PAHs tend to activate CAR, leading to the expression of respective target genes. Additionally, an increased PAH ring number is associated with AHR activation and DNA double-strand breaks, while smaller PAHs activate CAR but do not cause DNA damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Svenja Michalek, Thomas Brunner
Summary: LRH-1, an orphan nuclear receptor, plays a crucial role in regulating development, metabolism, and cancer by targeting mitochondria and associated activities. Its balanced expression contributes to maintaining physiological equilibrium, while deregulation may lead to inflammation and cancer. Researchers are exploring its potential as a pharmacological target for cancer therapy.
Article
Chemistry, Medicinal
Zuzana Rania Brozova, Jan Dusek, Norbert Palsa, Jana Maixnerova, Rajamanikkam Kamaraj, Lucie Smutna, Petr Matous, Albert Braeuning, Petr Pavek, Jiri Kunes, Nicholas Gathergood, Marcel Spulak, Milan Pour, Alejandro Carazo
Summary: A series of quinazolinone derivatives were synthesized and evaluated for their ability to selectively modulate human CAR activity. Several novel partial agonists and antagonists were identified, including 2-(3-methylphenyl) quinazolinone derivatives 7d and 8d as potent partial agonists. Compound 7l, a 2-(4-bromophenyl)quinazoline-4-thione, showed significant CAR antagonistic activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Alexandra A. Tsitrina, Noreen Halimani, Irina N. Andreichenko, Marat Sabirov, Mikhail Nesterchuk, Nataliya O. Dashenkova, Roman Romanov, Elena V. Bulgakova, Arsen Mikaelyan, Yuri Kotelevtsev
Summary: 4-methylumbelliferone (4MU) is a well-known inhibitor of hyaluronic acid synthesis and approved for cholestasis treatment. In animal models, 4MU has various effects including reducing inflammation, fibrosis, body weight, serum cholesterol, insulin resistance, as well as inhibiting tumor progression and metastasis. Through database analysis and transcriptome analysis, potential targets of 4MU were identified as enzymes and transcription factors, including members of the nuclear receptor superfamily. These findings suggest that 4MU has multiple targets and can regulate cell metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Christoph Wenzel, Lisa Goedtke, Anne Reichstein, Markus Keiser, Diana Busch, Marek Drozdzik, Stefan Oswald
Summary: This study aimed to characterize the gene expression and protein abundance of clinically relevant nuclear receptors in human intestine and liver. The results showed marked differences in the expression patterns of these nuclear receptors in the two organs, which may explain the different extent of unwanted drug-drug interactions depending on the administration route of drugs.
Article
Biochemistry & Molecular Biology
Joseph Wayne M. Fowler, Nabil E. Boutagy, Rong Zhang, Daiki Horikami, Michael B. Whalen, Casey E. Romanoski, William C. Sessa
Summary: The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and has been implicated in leukocyte immune responses. In this study, the role of SREBP2 in endothelial cells was investigated, revealing its impact on inflammatory chemokine production and interferon response genes.
JOURNAL OF LIPID RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Daniela Passarella, Maurizio Ronci, Valentina Di Liberto, Mariachiara Zuccarini, Giuseppa Mudo, Carola Porcile, Monica Frinchi, Patrizia Di Iorio, Henning Ulrich, Claudio Russo
Summary: Recent studies have found that cerebral cholesterol formation is primarily controlled by astrocytes, which synthesize cholesterol and deliver it to neurons and oligodendrocytes through specific lipoprotein receptors. Various proteins and carbohydrates modulate the cholesterol shuttle, affecting lipoprotein receptor activity, function, and signaling. Purine receptors, particularly subtypes P2Y(2), P2X(7), and A(2A), play a role in neurodegenerative diseases such as Alzheimer's and Niemann-Pick C diseases by regulating brain cholesterol homeostasis. The precise mechanisms of these interactions are not well understood, but further research in the cholesterol-purine reciprocal control is warranted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Joanna Dulinska-Litewka, Yoav Sharoni, Przemyslaw Halubiec, Agnieszka Lazarczyk, Oskar Szafranski, James A. McCubrey, Bartosz Gasiorkiewicz, Piotr Laidler, Torsten Bohn
Summary: Carotenoids, including lycopene and beta-carotene, play important roles in intra- and intercellular signaling, cell growth, and differentiation of prostate tissue. This review summarizes research on the role of carotenoids in prostate physiology and pathology over the past decade.
Article
Biochemistry & Molecular Biology
Anna Mukha, Eric Kalkhoven, Saskia W. C. van Mil
Summary: This review discusses the splice variants of metabolic nuclear receptors and their regulation of different metabolic pathways by nutritional signals. These NR splice variants add an intriguing new layer of complexity to metabolic signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)