Article
Biochemistry & Molecular Biology
Jacobus C. Buurstede, Susana N. Paul, Karolien De Bosscher, Onno C. Meijer, Jan Kroon
Summary: Glucocorticoids exert their effects by activating the glucocorticoid receptor (GR) throughout the body. This study investigated the interaction between glucocorticoids and androgen signaling in the liver transcriptome. The results showed that a substantial proportion of the hepatic transcriptome is androgen-dependent after chronic exposure, while the effects of glucocorticoids are largely androgen-independent after acute exposure. The study suggests that prolonged glucocorticoid exposure may upregulate androgen receptor expression, leading to androgen dependence not driven by direct interactions between the androgen receptor and glucocorticoid receptor.
Review
Medicine, Research & Experimental
Lijuan Mao, Wei Wei, Jingyu Chen
Summary: Glucocorticoids (GCs) are steroid hormones that regulate various homeostatic functions in the body through the binding of glucocorticoid receptor (GR). GR signals are biased, with variations in different tissue cells, disease states, and ligands. This bias regulation of GR signaling depends on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly, and intercellular differences. Selective GR agonists and modulators (SEGRAMs) have been developed to bias therapeutic outcomes towards expected effects by influencing GR-mediated gene expression. This paper reviews the bias regulation and mechanism of GR, as well as the progress in drug research.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Jane T. Seto, Kelly N. Roeszler, Lyra R. Meehan, Harrison D. Wood, Chrystal Tiong, Lucinda Bek, Siaw F. Lee, Manan Shah, Kate G. R. Quinlan, Paul Gregorevic, Peter J. Houweling, Kathryn N. North
Summary: Homozygosity for the common ACTN3 null polymorphism leads to deficiency in alpha-actinin-3, impacting sprint and power performance. Alpha-actinin-3 plays a critical role in regulating protein synthesis and breakdown in skeletal muscle, affecting muscle mass development. Deficiency in alpha-actinin-3 reduces the muscle wasting response to glucocorticoid dexamethasone, providing insights into the positive selection of the ACTN3 577X allele.
Article
Biology
Victor Bessonneau-Gaborit, Jonathan Cruard, Catherine Guerin-Charbonnel, Jennifer Derrien, Jean-Baptiste Alberge, Elise Douillard, Magali Devic, Sophie Deshayes, Loic Campion, Frank Westermann, Phillipe Moreau, Carl Herrmann, Jeremie Bourdon, Florence Magrangeas, Stephane Minvielle
Summary: This study generates multi-omics data and contact maps to investigate the genomic response and molecular mechanisms of dexamethasone (Dex) in multiple myeloma cells. The findings suggest that only a small portion of glucocorticoid receptor-binding sites are associated with enhancer activity gains and increased transcriptional activity. Furthermore, epigenomic changes and cell-to-cell transcriptional heterogeneity are observed in response to Dex.
LIFE SCIENCE ALLIANCE
(2023)
Article
Clinical Neurology
Darakhshan Jabeen Haleem
Summary: The global prevalence of depression is increasing, but the current treatment outcome is unsatisfactory. Stress-related epigenetic changes and the role of serotonin and 5-HT1A receptors in the pathogenesis and treatment of depression are important. Synthetic compounds targeting GC and 5-HT1A receptors may be better therapeutic agents for depression.
Article
Biochemistry & Molecular Biology
Yasukiyo Yoshioka, Shiori Oishi, Keita Onoda, Katsumi Shibata, Noriyuki Miyoshi
Summary: The study found that diosgenin is an effective functional food for preventing glucocorticoid-induced skeletal muscle atrophy. It acts by inhibiting protein expression, improving phosphorylation levels, and blocking nuclear translocation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Review
Pharmacology & Pharmacy
Fiorella Biasi, Valerio Leoni, Paola Gamba, Khouloud Sassi, Erard Lizard, Giuseppe Poli
Summary: The role of 27-hydroxycholesterol (27OHC) in cancer development varies across different types of cancer, with potential harmful effects in breast cancer but anti-cancer effects in prostate cancer. Increased synthesis of 27OHC may promote the progression of late-stage cancers in colon, brain, and thyroid tissues.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cell Biology
Ping Luo, Wenbo Feng, Shanshan Ma, Antao Dai, Kai Wu, Xianyue Chen, Qingning Yuan, Xiaoqing Cai, Dehua Yang, Ming-Wei Wang, H. Eric Xu, Yi Jiang
Summary: G protein-coupled receptors (GPCRs) are regulated by accessory proteins such as melanocortin receptor accessory protein 1 (MRAP1), which plays a crucial role in the regulation of melanocortin receptor 2 (MC2R). The activation of MC2R by adrenocorticotropic hormone (ACTH) and its involvement in glucocorticoid biogenesis have significant effects on the hypothalamic-pituitary-adrenal axis and related disorders. This study presents the cryo-electron microscopy structure of the ACTH-bound MC2R-G(s)-MRAP1 complex, revealing the unique structure and stabilizing effect of MRAP1 on ACTH binding and MC2R activation. The findings provide insights into GPCR regulation and the design of therapeutic agents targeting MC2R.
Review
Biochemistry & Molecular Biology
Yuchen Lei, Daniel. J. J. Klionsky
Summary: Macroautophagy/autophagy is a crucial catabolic pathway involved in maintaining cell homeostasis and promoting cell survival. Dysregulation of autophagy is linked to various human diseases, necessitating precise regulation at multiple levels to prevent inappropriate activity. This review focuses on the transcriptional regulation of autophagy, summarizing the transcription factors that control autophagy gene expression in yeast and mammalian cells. The association between changes in transcriptional regulation of autophagy and human pathophysiologies are also discussed.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Medicine, General & Internal
Wen Huang, Jin Zhou, Juanjuan Guo, Wen Hu, Guanghui Chen, Bin Li, Yajie Wen, Yimin Jiang, Kaili Fu, Huichang Bi, Yuanzhen Zhang, Hui Wang
Summary: Prenatal dexamethasone exposure can have lasting adverse effects on bile acid metabolism in offspring by affecting placental BA transporters and inducing imbalanced fetal-placental-maternal BA circulation, leading to increased levels of primary BAs in fetal serum.
Article
Oncology
Ying Zhou, Li Guan, Wei Li, Ruinan Jia, Lejiao Jia, Yuanyuan Zhang, Xin Wen, Sibo Meng, Daoxin Ma, Na Zhang, Min Ji, Yongjun Liu, Chunyan Ji
Summary: This study proposes an effective therapeutic regimen for T-cell acute lymphoblastic leukemia (T-ALL) by combining gamma-secretase inhibitors (GSIs) with dexamethasone (DEX) to overcome glucocorticoid resistance. Bone marrow targeting nanoparticles co-loaded with DEX and GSI were developed to enhance T-ALL cells recognition and endocytosis. In vitro and in vivo studies showed that this treatment significantly inhibited cell survival and promoted apoptosis of T-ALL cells, with high bone marrow accumulation and reduced toxicity. This study provides new strategies for the treatment of T-ALL and promising bone marrow targeting systems.
Article
Hematology
Duobing Zou, Mei Lv, Ying Chen, Tingting Niu, Chao Ma, Cong Shi, Zhenya Huang, Ying Wu, Shujun Yang, Yun Wang, Ningning Wu, Yi Zhang, Guifang Ouyang, Qitian Mu
Summary: Inhibiting MSI2 expression can effectively inhibit the proliferation and induce apoptosis of ALL cells. In addition, inhibiting MSI2 also increases the sensitivity of ALL cells to dexamethasone.
ANNALS OF HEMATOLOGY
(2023)
Review
Endocrinology & Metabolism
Nicolas C. Nicolaides
Summary: Glucocorticoid receptors play a crucial role in various cellular processes and physiological functions. Recent studies have shown that the beta isoform of the receptor, GR beta, has important functions in cellular homeostasis and is involved in endocrine physiology and pathophysiology.
Article
Biochemistry & Molecular Biology
Dabin Choi, Wesuk Kang, Soyoon Park, Bomin Son, Taesun Park
Summary: For several decades, excessive glucocorticoids (GCs) have been known to inhibit collagen synthesis and accelerate skin aging, but the molecular mechanisms involved are not well understood. In this study, the researchers identified potential glucocorticoid receptor (GR) target genes that may contribute to the inhibition of collagen synthesis. They confirmed that dexamethasone, a synthetic GC, activates canonical GR signaling in dermal fibroblasts and identified six candidate genes involved in the GC-mediated inhibition of collagen synthesis. This study provides insights into the molecular mechanisms of GC-mediated skin aging and lays the foundation for further research on the biological characteristics of individual GR target genes.
Article
Pharmacology & Pharmacy
Dingmei Zhang, Kexin Liu, Wen Hu, Xiaoqian Lu, Li Li, Qi Zhang, Hegui Huang, Hui Wang
Summary: This study confirmed that dexamethasone induces cell autophagy by activating the GR- FOXO1 pathway in utero, inhibiting hepatocyte proliferation and causing liver dysplasia in offspring rats.
Article
Biochemistry & Molecular Biology
Grzegorz Wicher, Maria Norlin
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Maria Norlin, Hanna Pettersson, Wanjin Tang, Kjell Wikvall
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2011)
Article
Biochemistry & Molecular Biology
Johan Lundqvist, Kjell Wikvall, Maria Norlin
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2012)
Article
Biochemistry & Molecular Biology
Hanna Pettersson, Johan Lundqvist, Ernst Oliw, Maria Norlin
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2009)
Article
Biochemistry & Molecular Biology
Hanna Pettersson, Johan Lundqvist, Maria Norlin
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2010)
Article
Biochemistry & Molecular Biology
Johan Lundqvist, Maria Norlin, Kjell Wikvall
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2010)
Article
Biochemistry & Molecular Biology
Johan Lundqvist, Maria Norlin, Kjell Wikvall
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2011)
Article
Biochemistry & Molecular Biology
Johan Lundqvist, Maria Norlin
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2012)
Article
Pharmacology & Pharmacy
Maria Ellfolk, Maria Norlin, Katarina Gyllensten, Kjell Wikvall
MOLECULAR PHARMACOLOGY
(2009)
Article
Biochemistry & Molecular Biology
Asa Fex Svenningsen, Grzegorz Wicher, Johan Lundqvist, Hanna Pettersson, Mikael Corell, Maria Norlin
NEUROCHEMISTRY INTERNATIONAL
(2011)
Article
Neurosciences
Ida Emanuelsson, Maria Norlin
NEUROSCIENCE LETTERS
(2012)
Review
Endocrinology & Metabolism
Maria Norlin
JOURNAL OF NEUROENDOCRINOLOGY
(2020)
Article
Cell Biology
Ahmad Zayny, Mokhtar Almokhtar, Kjell Wikvall, Osten Ljunggren, Kumari Ubhayasekera, Jonas Bergquist, Pinar Kibar, Maria Norlin
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Maria Norlin, Kjell Wikvall
Summary: Vitamin D signaling plays a crucial role in maintaining calcium balance for bone health and has various functions in different tissues. Disturbances in vitamin D signaling are associated with numerous diseases. This review focuses on the identification of bioactivating enzymes and their genes involved in the production of active vitamin D metabolites. It evaluates species- and tissue-specific expression, enzyme kinetics, substrate specificity, and the consequences of gene mutations. The roles of different vitamin D receptors and alternative bioactivation pathways are also discussed. Although significant progress has been made in understanding vitamin D bioactivation enzymes, further research is needed to fully comprehend the pleiotropic effects and the mechanisms of enzymatic activation in vitamin D-induced responses.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Frida Olsson, Niki Sarri, Natalia Papadopoulos, Johan Lennartsson, Maria Norlin
Summary: The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3, has been found to suppress the growth and signaling pathways of cancer cells, making it a potential treatment for brain cancer such as glioblastoma. This study showed that 1 alpha,25-dihydroxyvitamin D-3 and the vitamin D analog tacalcitol can inhibit the growth and metastatic potential of glioblastoma cells, indicating their potential as therapeutic agents for brain cancer.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Chenchen Bian, Xiangtong Yuan, Caihong Zeng, Jian Sun, Gen Kaneko, Hong Ji
Summary: This study investigated the mechanism of docosahexaenoic acid (DHA)-induced apoptosis mediated by mitophagy, using grass carp as an animal model. The results showed that inhibition of mitophagy alleviated apoptosis and eliminated the inhibition of lipid accumulation induced by DHA. Mechanistically, DHA induced mitophagy by activating the PPAR gamma-LC3-BNIP3 pathway. Inhibition of PPAR gamma decreased autophagy-related gene expression and prevented BNIP3/NIX-mediated mitophagy-induced apoptosis, thereby alleviating the inhibition of lipid accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Venkatesan Ramya, Karuppiah Prakash Shyam, Arulanandu Angelmary, Balamuthu Kadalmani
Summary: This study reveals that Lauric acid (LA) exerts an epigenetic regulation and metabolic reprogramming on SH-SY5Y neuroblastoma cells through modulation of lncRNA HOTAIR, remodeling of chromatin H3K4 tri-methylation and regulation of glucose uptake by controlling NF-kappa B activation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Sreelekshmi Sreekumar, Karyath Palliyath Gangaraj, Manikantan Syamala Kiran
Summary: This study investigates the intricate interplay between angiogenic regulation and the browning of white adipocytes. The findings reveal that concurrent activation of angiogenesis is necessary for inducing browning of white adipocytes. The study also highlights the role of Vascular endothelial growth factor (VEGF) in promoting angiogenesis and triggering the browning process through the activation of Estrogen receptor alpha (ER alpha) signaling pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Zanxia Cao, Liling Zhao, Mingcui Chen, Zhihong Shi, Lei Liu
Summary: This study investigated the translocation process of cholesterol/calcitriol in bacterial membranes and their effects on membrane structure. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. These findings contribute to a better understanding of the relationship between cholesterol/calcitriol concentrations, lipid bilayer structure, and water permeation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Xiaozhen Guo, Jiawen Wang, Hualing Xu, Yangyang Wang, Yutang Cao, Yingquan Wen, Jiaqi Li, Yameng Liu, Kanglong Wang, Jue Wang, Xianchun Zhong, Chuying Sun, Yongxin Zhang, Jingyi Xu, Cuina Li, Pengxiang Mu, Lingyan Xu, Cen Xie
Summary: This study aims to investigate the role of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis and assess the impact of obesity on them. The results show that high fat diet feeding and Leptin gene deficiency disrupt the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The study provides compelling evidence for the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis, and elucidates the deleterious effects of obesity on gut microbiome-bile acid metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Maria Cotugno, Federico Marracino, Luca Capocci, Ludovica Pizzati, Maurizio Forte, Rosita Stanzione, Pamela Scarselli, Alba Di Pardo, Sebastiano Sciarretta, Massimo Volpe, Speranza Rubattu, Vittorio Maglione
Summary: The study found that enzymes involved in sphingolipid metabolism show abnormal expression in the cardiac tissue of hypertensive rat models, which may be related to the susceptibility to cardiac damage.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)