Article
Plant Sciences
Xiaochen Jia, Hongyan Zhang, Hongqiang Qin, Kuikui Li, Xiaoyan Liu, Wenxia Wang, Mingliang Ye, Heng Yin
Summary: In this study, a functional plant AGM (AtAGM) was identified from Arabidopsis thaliana, with a significant role in UDP-GlcNAc biosynthesis pathway. AtAGM catalyzes the isomerization of GlcNAc-1-P and GlcNAc-6-P, and has broad catalytic activity on different phosphohexoses. The decrease in UDP-GlcNAc content in AtAGM mutants resulted in impaired protein O-GlcNAcylation and temperature-dependent growth defects in seedlings.
Review
Genetics & Heredity
Alysta Paneque, Harvey Fortus, Julia Zheng, Guy Werlen, Estela Jacinto
Summary: The article summarizes the importance of uridine diphosphate-N-acetyl glucosamine (UDP-GlcNAc) produced by the hexosamine biosynthesis pathway (HBP) in the glycosylation of proteins. It discusses the pathways for hexosamine production, including de novo and salvage mechanisms, and the regulation of HBP by various signaling molecules and environmental factors. The article also examines the role of UDP-GlcNAc in protein glycosylation, proteostasis maintenance, nutrient availability, and cell signaling, as well as the implications of deregulated N-glycosylation and O-GlcNAcylation in diseases. It further reviews the current pharmacological strategies targeting HBP enzymes and the potential therapeutic efficacy of engineered prodrugs.
Review
Endocrinology & Metabolism
Amber Lockridge, John A. Hanover
Summary: The O-GlcNAc regulatory system interacts extensively with lipids and is essential for maintaining lipid homeostasis. Hyperlipidemia affects O-GlcNAc levels through various mechanisms and is associated with obesity and metabolic dysregulation.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yuanjiao Yang, Yunlong Chen, Shiya Zhao, Huipu Liu, Jingxing Guo, Huangxian Ju
Summary: This study developed a quantitative SERS imaging strategy for mapping the O-GlcNAcylation distribution of single living cells. O-GlcNAcylated compounds (OGCs) were quantified through in situ azide labeling and a click reaction, allowing for convenient detection of OGCs in different areas of single living cells using a calibration curve obtained in vitro. This method demonstrated its practicality and expansibility in glycosylation related analysis through successfully mapping O-GlcNAcylation distribution in different cell lines and monitoring O-GlcNAcylation variation during the cell cycle.
Article
Multidisciplinary Sciences
Victoria Palin, Matthew Russell, Robert Graham, John D. Aplin, Melissa Westwood
Summary: Women with pre-existing diabetes have altered placental O-GlcNAcome, potentially affecting fetal growth, indicating that the maternal metabolic environment in diabetes can impact the placental response to clathrin-mediated endocytosis.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Brenna M. Zimmer, Joseph J. Barycki, Melanie A. Simpson
Summary: Hyaluronan is a versatile macromolecule that plays a critical role in various functions such as cushioning, hydration, and signaling. Its production is regulated at multiple levels, including epigenetic, transcriptional, and posttranslational control. The availability of precursor molecules affects the rate and amount of hyaluronan synthesis. The sugar substrates for hyaluronan synthesis also participate in finely-tuned pathways that intersect with other metabolic processes. Dysregulation of nucleotide sugar and hyaluronan synthesis is associated with various diseases, making these pathways potential targets for therapeutic intervention.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Eugenia Wulff-Fuentes, Rex R. Berendt, Logan Massman, Laura Danner, Florian Malard, Jeet Vora, Robel Kahsay, Stephanie Olivier-Van Stichelen
Summary: Over the past 35 years, extensive research has been conducted on protein O-GlcNAcylation, resulting in the establishment of a database of human O-GlcNAcylated proteins and the acquisition of a more robust semi-consensus sequence through analysis. Additionally, a comprehensive meta-analysis of human O-GlcNAcylated proteins has revealed that O-GlcNAcylation is a master regulator of cell signaling.
Article
Multidisciplinary Sciences
Akihito Ishikita, Shouji Matsushima, Soichiro Ikeda, Kosuke Okabe, Ryohei Nishimura, Tomonori Tadokoro, Nobuyuki Enzan, Taishi Yamamoto, Masashi Sada, Yoshitomo Tsutsui, Ryo Miyake, Masataka Ikeda, Tomomi Ide, Shintaro Kinugawa, Hiroyuki Tsutsui
Summary: The molecular mechanisms of cardiac hypertrophy induced by glucose metabolism remain incompletely understood. The Hexosamine biosynthesis pathway (HBP) plays a key role in mediating cardiac hypertrophy through protein O-GlcNAcylation and Akt activation. GFAT2, a critical enzyme in the HBP pathway, is identified as a major isoform in the heart and is involved in regulating cardiomyocyte hypertrophy.
Review
Cell Biology
Vivian Lu, Irena J. Roy, Michael A. Teitell
Summary: Pluripotent stem cells are influenced by nutrients provided in the medium, which affect their self-renewal, lineage specification, and earliest differentiation. Research is actively investigating which specific nutrients support these outcomes and their mechanisms of action in this rapidly expanding field of study.
Article
Endocrinology & Metabolism
Rinaldo Rodrigues dos Passos Junior, Raiany Alves de Freitas, Vanessa Dela Justina, Sebastian San Martin, Victor Vitorino Lima, Fernanda Regina Giachini
Summary: This study found that insufficient protein O-GlcNAcylation caused by decreased placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemical Research Methods
Zhiqiang Xiao, Yongtong Wang, Juan Liu, Siqi Zhang, Xinjia Tan, Yifei Zhao, Jiwei Mao, Ning Jiang, Jingwen Zhou, Yang Shan
Summary: In this study, a biosynthetic pathway for flavonoid-7-O-disaccharide was constructed in Saccharomyces cerevisiae using metabolic engineering and promoter strategies. The optimized strain produced high yields of various flavonoid-7-O-disaccharides, making it the first report on the biosynthesis of flavonoid-7-O-disaccharide.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Oncology
Christine Lam, Jin-Yih Low, Phuoc T. Tran, Hailun Wang
Summary: The hexosamine biosynthetic pathway (HBP) is a glucose metabolism pathway that results in the synthesis of UDP-GlcNAc, which can be used for post-translational modification of intracellular proteins. Activation of HBP has been implicated in cancer pathophysiology, and inhibition of HBP enzymes may serve as a novel strategy for cancer treatment by suppressing tumor growth and modulating immune response. Targeting HBP could potentially enhance sensitivity of tumor cells to conventional cancer therapy.
Article
Biochemistry & Molecular Biology
Mackenzie Moore, Nandini Avula, Seokwon Jo, Megan Beetch, Emilyn U. Alejandro
Summary: The study found that offspring with a partial reduction in placental OGT showed reduced weight gain and improved insulin tolerance under a high-fat diet challenge, possibly due to increased hepatic insulin signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Sumita Mishra, Junfeng Ma, Desirae McKoy, Masayuki Sasaki, Federica Farinelli, Richard C. Page, Mark J. Ranek, Natasha Zachara, David A. Kass
Summary: This study reveals that the calcium channel TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus, and this O-GlcNAcylation plays a critical role in regulating TRPC6 channel conductance and NFAT activation.
Review
Cell Biology
Kamau M. M. Fahie, Kyriakos N. Papanicolaou, Natasha E. Zachara
Summary: The modification of proteins by O-GlcNAc is an essential post-translational modification that plays a key role in cellular stress response, particularly in the cardiovascular system and neurodegenerative diseases.
Review
Physiology
John C. Chatham, Jianhua Zhang, Adam R. Wende
Summary: The discovery of O-GlcNAcylation in the mid-1980s challenged the conventional notion of glycosylation and its impact on cellular functions. Dysregulation in O-GlcNAc cycling has been implicated in the progression of various diseases.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Physiology
Thomas Dupas, Manon Denis, Justine Dontaine, Antoine Persello, Laurent Bultot, Angelique Erraud, Didier Vertommen, Bertrand Bouchard, Arnaud Tessier, Matthieu Riviere, Jacques Lebreton, Edith Bigot-Corbel, Jerome Montnach, Michel De Waard, Chantal Gauthier, Yan Burelle, Aaron K. Olson, Bertrand Rozec, Christine Des Rosiers, Luc Bertrand, Tarik Issad, Benjamin Lauzier
Summary: The study found that protein O-GlcNAc levels decrease significantly and progressively from birth to adulthood in the heart, while the changes in liver and brain are opposite. O-GlcNAc levels are minimally affected by weaning diet, and changes in regulatory enzymes and metabolites levels are tissue-specific. Mass spectrometry identified potential O-GlcNAcylated proteins in the heart, suggesting a specific role for these proteins in the development process.
Article
Cardiac & Cardiovascular Systems
Darnel Prakoso, Shiang Y. Lim, Jeffrey R. Erickson, Rachel S. Wallace, Jarmon G. Lees, Mitchel Tate, Helen Kiriazis, Daniel G. Donner, Darren C. Henstridge, Jonathan R. Davey, Hongwei Qian, Minh Deo, Laura J. Parry, Amy J. Davidoff, Paul Gregorevic, John C. Chatham, Miles J. De Blasio, Rebecca H. Ritchie
Summary: Elevated protein O-GlcNAc modification is observed in diabetic human myocardium, and selectively targeting cardiac protein O-GlcNAcylation may offer a new therapeutic approach for diabetes-induced heart failure. In non-diabetic mice, rAAV6-OGT impairs LV diastolic function and induces maladaptive cardiac remodelling, while rAAV6-OGA rescues LV diastolic function and adverse cardiac remodelling in diabetic mice.
CARDIOVASCULAR RESEARCH
(2022)
Article
Pharmacology & Pharmacy
John C. Chatham, Martin E. Young, Jianhua Zhang
Summary: This review discusses the post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) in the cardiovascular system, and how dysregulation in O-GlcNAc cycling may contribute to the adverse effects of diabetes on the cardiovascular system.
CURRENT OPINION IN PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Mary N. Latimer, Ravi Sonkar, Sobuj Mia, Isabelle Robillard Frayne, Karen J. Carter, Christopher A. Johnson, Samir Rana, Min Xie, Glenn C. Rowe, Adam R. Wende, Sumanth D. Prabhu, Stuart J. Frank, Christine Des Rosiers, John C. Chatham, Martin E. Young
Summary: The timing of BCAA consumption has significant implications for cardiac health and disease, with intake at the end of the active period resulting in increased cardiac protein synthesis and mass, and enlarged cardiomyocytes, while intake at the beginning of the active period has no effect.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Physiology
Helen E. Collins, Joshua C. Anderson, Adam R. Wende, John C. Chatham
Summary: This study discovered that STIM1 regulates the activity of calcium-dependent kinases and phosphatases in adult mouse hearts. This has important implications for understanding the role of STIM1 in cardiac physiology and pathophysiology.
PHYSIOLOGICAL REPORTS
(2022)
Article
Neurosciences
Van N. Huynh, Gloria A. Benavides, Michelle S. Johnson, Xiaosen Ouyang, Balu K. Chacko, Edie Osuma, Toni Mueller, John Chatham, Victor M. Darley-Usmar, Jianhua Zhang
Summary: The accumulation of neurotoxic proteins in age-related neurodegenerative diseases is associated with metabolic and mitochondrial dysfunction. The hexosamine biosynthesis pathway, specifically O-GlcNAcylation, has been proposed as a therapeutic target. In this study, the correlation between O-GlcNAcylation factors and mitochondrial function, autophagy/lysosomal pathways, and neurodegenerative disease-related proteins was investigated. Sex and TG-dependent differences were observed in these associations. This research provides insights into the interconnectivity of O-GlcNAc-dependent pathways in brain aging and neurodegenerative pathogenesis, as well as potential treatment responses.
Article
Biochemistry & Molecular Biology
Margaret B. Bell, Xiaosen Ouyang, Abigail K. Shelton, Nha V. Huynh, Toni Mueller, Balu K. Chacko, Anil G. Jegga, John C. Chatham, C. Ryan Miller, Victor Darley-Usmar, Jianhua Zhang
Summary: Enhancing protein O-GlcNAcylation by pharmacological inhibition of O-GlcNAcase (OGA) has been explored in mouse models of amyloid-beta and tau pathology. The link between O-GlcNAcylation, gene expression, and neurological behavior was examined using Thiamet G (TG) as an OGA inhibitor. TG-treated mice showed improved working memory, and RNA sequencing analysis revealed differentially expressed genes related to learning, cognition, and behavior.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Physiology
Xiaosen Ouyang, Sayan Bakshi, Gloria A. A. Benavides, Zhihuan Sun, Gerardo Hernandez-Moreno, Helen E. E. Collins, Mariame S. S. Kane, Silvio Litovsky, Martin E. E. Young, John C. C. Chatham, Victor Darley-Usmar, Adam R. R. Wende, Jianhua Zhang
Summary: Autophagy plays a crucial role in maintaining the quality of proteins and organelles. The expression of autophagy is tightly regulated by transcriptional mechanisms, including the repression of ZKSCAN3. In this study, ZKSCAN3 knockout in cardiomyocytes disrupted the balance between autophagy activation and repression, exacerbating cardiac remodeling in response to pressure overload. These findings suggest that ZKSCAN3 plays a critical role in regulating autophagy and cardiac remodeling in the context of pressure overload.
PHYSIOLOGICAL REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Luyun Zou, Dingguo Zhang, Chae-Myeong Ha, Adam R. Wende, John C. Chatham
Summary: By optimizing the protocol, we successfully obtained O-GlcNAc-positive staining of proteins in cardiac tissue while minimizing nonspecific staining.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Chae-Myeong Ha, Sayan Bakshi, Manoja K. Brahma, Luke A. Potter, Samuel F. Chang, Zhihuan Sun, Gloria A. Benavides, Lihao He, Prachi Umbarkar, Luyun Zou, Samuel Curfman, Sini Sunny, Andrew J. Paterson, Namakkal-Soorappan Rajasekaran, Jarrod W. Barnes, Jianhua Zhang, Hind Lal, Min Xie, Victor M. Darley-Usmar, John C. Chatham, Adam R. Wende
Summary: This study indicates that moderate increases in cardiomyocyte protein O-GlcNAcylation leads to a differential response with an initial reduction of metabolic pathways (2-week), which leads to cardiac remodeling (24-week). Moreover, the mouse model showed evidence of diastolic dysfunction consistent with a heart failure with preserved ejection fraction.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Biochemical Research Methods
John C. Chatham, Chae-Myeong Ha, Adam R. Wende
Summary: In this issue of Cell Reports Methods, Sunden et al. introduce an enzymatic assay for measuring UDP-GlcNAc levels in cells and tissue. This approach provides insights into the concentration of UDP-GlcNAc under different conditions, thus enhancing the field's understanding.
CELL REPORTS METHODS
(2023)
Review
Geriatrics & Gerontology
Helen E. Collins, Dingguo Zhang, John C. Chatham
Summary: The tight regulation of intracellular calcium ions is crucial for various cellular functions. This review focuses on the molecular regulation and roles of STIM and Orai proteins, which are involved in calcium signaling and have implications in heart disease and neurodegeneration.
FRONTIERS IN AGING
(2022)
Article
Geriatrics & Gerontology
Van N. Huynh, Sheng Wang, Xiaosen Ouyang, Willayat Y. Wani, Michelle S. Johnson, Balu K. Chacko, Anil G. Jegga, Wei-Jun Qian, John C. Chatham, Victor M. Darley-Usmar, Jianhua Zhang
Summary: O-GlcNAcylation plays a role in potential therapeutic targets for neurodegenerative diseases, with Thiamet G (TG) impacting this protein modification. The study shows that TG leads to an increase in O-GlcNAcylation, particularly in synaptic proteins, trafficking, signaling pathways, etc.
FRONTIERS IN AGING
(2021)
Review
Geriatrics & Gerontology
Helen E. Collins, Mariame Selma Kane, Silvio H. Litovsky, Victor M. Darley-Usmar, Martin E. Young, John C. Chatham, Jianhua Zhang
Summary: Transmission electron microscopy (TEM) is a crucial technique for studying cardiac ultrastructural changes, particularly in cardiovascular development, aging, and pathology. TEM allows visualization and study of various signaling processes that impact mitochondrial function.
FRONTIERS IN AGING
(2021)