Article
Cell Biology
Jianqiu Zou, Wenjuan Wang, Yi Lu, Juan Ayala, Kunzhe Dong, Hongyi Zhou, Jinxi Wang, Weiqin Chen, Neal L. Weintraub, Jiliang Zhou, Jie Li, Huabo Su
Summary: Cardiac maturation is regulated by neddylation, a post-translational modification process. Mosaic deletion of NAE1, a necessary enzyme for neddylation, in neonatal hearts leads to cardiomyopathy and heart failure. Neddylation is involved in transverse tubule formation, physiological hypertrophy, and fetal-to-adult isoform switching, promoting cardiac maturation through oxidative metabolism.
Review
Cell Biology
Nasim Kheshtchin, Jamshid Hadjati
Summary: Hypoxia, a common characteristic of solid tumors, contributes to different aspects of tumor progression and limits the efficacy of immunotherapies. Developing new immunotherapy strategies involving therapeutic targeting of HIF-1 molecules associated with hypoxia may enhance the clinical effectiveness of immunotherapy. Targeting hypoxia presents a potential opportunity to improve the clinical benefit of cancer immunotherapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Xinguo Jiang, Wen Tian, Dongeon Kim, Alexander S. McQuiston, Ryan Vinh, Stanley G. Rockson, Gregg L. Semenza, Mark R. Nicolls
Summary: Lymphedema is a chronic inflammatory disorder with incomplete understanding of its pathology and lack of approved pharmacological therapy. Studying hypoxia-regulated pathways in lymphedema may lead to new treatment approaches.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Thuy-Hang Nguyen, Stephanie Conotte, Alexandra Belayew, Anne-Emilie Decleves, Alexandre Legrand, Alexandra Tassin
Summary: Muscular dystrophies are genetic degenerative muscle disorders characterized by muscle wasting, often accompanied by respiratory impairments and hypoxemia. Hypoxic stress activates compensatory mechanisms, with HIF-1α playing a key role. Alterations in HIF-1α in muscle may impact the pathophysiology of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Daniela Mennerich, Kateryna Kubaichuk, Ghulam S. Raza, Dominik C. Fuhrmann, Karl-Heinz Herzig, Bernhard Bruene, Thomas Kietzmann
Summary: Metabolic adaptation and signal integration in response to hypoxia is regulated by hypoxia-inducible factors (HIFs). This study shows that high fat diet-induced endoplasmic reticulum stress attenuates the response to hypoxia by promoting the degradation of HIF-1 and HIF-2 through GSK3 beta and the ubiquitin ligase FBXW1A/beta TrCP, leading to decreased proliferation, migration, and increased sensitivity to ER stress-induced apoptosis. Moreover, hypoxia affects the ER stress response mainly through the PERK-arm of the unfolded protein response (UPR).
Article
Gastroenterology & Hepatology
Peter A. C. Wing, Peter Jianrui Liu, James M. Harris, Andrea Magri, Thomas Michler, Xiaodong Zhuang, Helene Borrmann, Rosalba Minisini, Nicholas R. Frampton, Jochen M. Wettengel, Laurent Mailly, Valentina D'Arienzo, Tobias Riedl, Luis Nobre, Michael P. Weekes, Mario Pirisi, Mathias Heikenwalder, Thomas F. Baumert, Ester M. Hammond, David R. Mole, Ulrike Protzer, Peter Balfe, Jane A. McKeating
Summary: HIFs play a crucial role in regulating HBV replication, revealing an evolutionary mechanism by which HBV exploits the HIF signaling pathway to persist in the low oxygen environment of the liver.
JOURNAL OF HEPATOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Xiao-Yi Chen, Qian-Long Wang, Wei-Xue Huang, Long-Wei Li, Lan-Cong Liu, Yi Yang, You-Jiao Wu, Shan-Shan Song, Hao Ma, Hua Zhou, Pei Luo
Summary: This study aimed to analyze and evaluate the dynamic changes in HIF-1 alpha concentration in serum exosomes during bacterial peritonitis. A new colorimetric method to quantitate these changes was established. The results showed that the serum exosomal HIF-1 alpha levels increased in the early stage of bacterial peritonitis, reached a peak at 24-48 hours, and then gradually decreased. Intervention treatment reduced the abdominal infection extent, HIF-1 alpha concentration in serum exosomes, and the serum pro-inflammatory factors levels. These findings suggest that serum exosomal HIF-1 alpha can be used as a biomarker for predicting and monitoring the pathological process of bacterial peritonitis.
Review
Cell Biology
Mykyta Malkov, Chee Teik Lee, Cormac T. Taylor
Summary: Hypoxia and inflammation frequently co-occur in inflammatory diseases, with pro-inflammatory cytokines such as TNF-alpha and IL-1 beta directly impacting HIF signaling pathways. Multi-level crosstalk between inflammatory and hypoxic signaling pathways plays a crucial role in shaping the degree of inflammation at hypoxic sites.
Review
Immunology
Tineke Vanderhaeghen, Rudi Beyaert, Claude Libert
Summary: Glucocorticoid-induced and hypoxia-induced transcriptional responses play crucial roles in maintaining tissue homeostasis and regulating cellular stress and inflammatory responses. Cells respond rapidly to hypoxia to prevent metabolic shutdown and death through hypoxia inducible factors (HIFs). The crosstalk between the glucocorticoid receptor (GR) and HIFs has been investigated, and the therapeutic effects of GCs on HIF-mediated diseases have been discussed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Alina Mihaela Stanigut, Camelia Pana, Manuela Enciu, Mariana Deacu, Bogdan Cimpineanu, Liliana Ana Tuta
Summary: Research has found that hypoxia response and hypoxia-inducible factors play critical roles in the pathogenesis of diabetic nephropathy, and HIF stabilizers are considered as novel therapeutic agents for treating anemia in CKD patients and relieving oxidative stress in renal tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Virology
David A. Davis, Prabha Shrestha, Robert Yarchoan
Summary: The complex interactions between Kaposi sarcoma-associated herpesvirus (KSHV), hypoxia, and hypoxia-inducible factors (HIFs) play important roles in the pathogenesis of KSHV-induced diseases. Interfering with HIFs can decrease tumor growth and induce death of infected cells and KSHV-induced tumors, providing novel strategies for the treatment of KSHV-induced diseases.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Chemistry, Physical
Zheng Wang, Xuewen Mu, Qian Yang, Jiajia Luo, Yanjun Zhao
Summary: This study utilizes hypoxia-responsive polymer micelles combined with an NQO1 inhibitor (dicoumarol) to enhance the sensitivity of ovarian cancer cells to the anticancer drug sorafenib under low oxygen conditions. Both drugs are encapsulated in nanoscale micelles and the degradation of HIF-1α is increased to improve apoptosis induced by the drug.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Kenta Kaihara, Shuji Nakagawa, Yuji Arai, Hiroaki Inoue, Shinji Tsuchida, Yuta Fujii, Yoichiro Kamada, Tsunao Kishida, Osam Mazda, Kenji Takahashi
Summary: The study found that hypoxia can suppress the development of rheumatoid arthritis by controlling HIF-1 alpha expression, delaying joint swelling and reducing joint destruction. Deferoxamine-mediated activation of HIF-1 alpha can counteract the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Dan Du, Yugang Zhang, Canjun Zhu, Hong Chen, Jia Sun
Summary: The earliest function of hypoxia-inducible factor (HIF) was to respond to hypoxic conditions as a transcription factor. Recent studies have shown that HIF plays an essential role in central regulation of metabolism, affecting the central nervous system's response to glucose, inflammation, and hormonal influence on systemic metabolism. HIF primarily inhibits energy uptake and promotes energy expenditure in the hypothalamus, with its role depending on various factors and mechanisms within the hypothalamus.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yu-Kun Jie, Jian-Jun Jiang, Hong-Ling Ma, Chang -Hong Cheng, Guang-Xin Liu, Si-Gang Fan, Juan Feng, Zhi-Xun Guo
Summary: In this study, a novel PHD2 gene, SpPHD2, was cloned and identified in the mud crab Scylla paramamosain. The mRNA expression of SpPHD2 was widely distributed across all examined tissues, and the protein was mainly localized in the cytoplasm. Silencing SpPHD2 in vivo upregulated SpHIF-1 alpha and downstream genes, while overexpression of SpPHD2 in vitro dose-dependently reduced SpHIF-1 alpha transcriptional activity, indicating the crucial role of SpPHD2 in regulating SpHIF-1 alpha.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Maria Juarez-Fernandez, Naroa Goikoetxea-Usandizaga, David Porras, Maria Victoria Garcia-Mediavilla, Miren Bravo, Marina Serrano-Macia, Jorge Simon, Teresa C. Delgado, Sofia Lachiondo-Ortega, Susana Martinez-Florez, Oscar Lorenzo, Mercedes Rincon, Marta Varela-Rey, Leticia Abecia, Hector Rodriguez, Juan Anguita, Esther Nistal, Maria Luz Martinez-Chantar, Sonia Sanchez-Campos
Summary: This study provides evidence for the relevance of the interaction between mitochondria and microbiota in NASH and identifies targeting this interaction as a valuable therapeutic approach.
Article
Multidisciplinary Sciences
Aaron E. Robinson, Aleksandra Binek, Komal Ramani, Niveda Sundararaman, Lucia Barbier-Torres, Ben Murray, Vidya Venkatraman, Simion Kreimer, Angela Mc Ardle, Mazen Noureddin, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Virginia Gutierrez de Juan, Oscar Millet, Jose M. Mato, Shelly C. Lu, Jennifer E. Van Eyk
Summary: Methionine adenosyltransferase 1a (MAT1A) gene is responsible for the synthesis of hepatic S-adenosyl-L-methionine (SAMe). Deficiency of MAT1A results in hepatic SAMe depletion and development of nonalcoholic steatohepatitis (NASH), which can be reversed by SAMe administration. In this study, alterations in the proteome/phosphoproteome were examined in pre-disease and NASH Mat1a(-/-) mice, and compared to human nonalcoholic fatty liver disease (NAFLD). Common proteomic/phosphoproteomic signatures and metabolomic characteristics were found betweenMat1a(-/-) mice and a specific subtype of human NAFLD, suggesting potential implications for pathophysiology and therapy.
Review
Biochemistry & Molecular Biology
Beatrice Foglia, Marc Beltra, Salvatore Sutti, Stefania Cannito
Summary: Hepatocellular carcinoma (HCC) is a common primary liver cancer, ranking third in cancer-related mortality worldwide. Metabolic rewiring has emerged as a key factor in HCC progression, affecting cancer cell behavior and immune responses. This review focuses on recent studies exploring HCC's metabolic traits, specifically alterations in glucose, fatty acid, and amino acid metabolism. Additionally, it examines how metabolic reprogramming can impact the tumor microenvironment and immune cell populations, enabling tumor escape from immunosurveillance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Anna Maria Tolomeo, Gaia Zuccolotto, Ricardo Malvicini, Giada De Lazzari, Alessandro Penna, Chiara Franco, Federico Caicci, Fabio Magarotto, Santina Quarta, Michela Pozzobon, Antonio Rosato, Maurizio Muraca, Federica Collino
Summary: This study aimed to evaluate the biodistribution of MSC-EVs after different routes of administration in mice. Results showed that local administration could increase the concentration of EVs in selective organs, limiting their systemic distribution and potentially reducing extra-organ effects. Biodistribution studies can help in selecting the most appropriate way of administering MSC-EVs for treating different diseases.
Article
Biochemistry & Molecular Biology
Alessandra Biasiolo, Michele Sandre, Stefania Ferro, Santina Quarta, Mariagrazia Ruvoletto, Gianmarco Villano, Cristian Turato, Maria Guido, Oriano Marin, Patrizia Pontisso
Summary: This study aimed to generate antibodies against different SerpinB3 epitopes to better understand their biological role. Five exposed epitopes were identified and corresponding synthetic peptides were used for rabbit immunization. Anti-P#2 and anti-P#4 antibodies could recognize both SerpinB3 and SerpinB4, while anti-P#5 antibody showed the greatest specific reactivity for human SerpinB3 and could recognize SerpinB3 at the nuclear level.
Article
Biochemistry & Molecular Biology
Saadet Turkseven, Cristian Turato, Gianmarco Villano, Mariagrazia Ruvoletto, Maria Guido, Massimo Bolognesi, Patrizia Pontisso, Marco Di Pascoli
Summary: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease that can progress to non-alcoholic steatohepatitis (NASH) and eventually cirrhosis. Inflammation and oxidative stress, caused by mitochondrial dysfunction, are crucial in the development of NASH. This study evaluated the potential of acetylsalicylic acid (ASA) and mitoquinone, an antioxidant, to inhibit the progression of NASH. The results showed that both ASA and mitoquinone reduced liver steatosis and inflammation, restored anti-inflammatory factors, and increased antioxidant expression.
Article
Biology
Santina Quarta, Andrea Cappon, Cristian Turato, Mariagrazia Ruvoletto, Stefania Cannito, Gianmarco Villano, Alessandra Biasiolo, Maristella Maggi, Francesca Protopapa, Loris Bertazza, Silvano Fasolato, Maurizio Parola, Patrizia Pontisso
Summary: This study investigates the ability of SerpinB3 to modulate the Wnt pathway in liver cancer and monocytic cells, finding that SerpinB3 activates the Wnt signaling pathway and increases cell survival and invasiveness through the upregulation of Wnt co-receptors and LRP family members.
Article
Endocrinology & Metabolism
Maria J. Gonzalez-Rellan, Tamara Parracho, Violeta Heras, Amaia Rodriguez, Marcos F. Fondevila, Eva Novoa, Natalia Lima, Marta Varela-Rey, Ana Senra, Maria D. P. Chantada-Vazquez, Cristina Ameneiro, Ganeko Bernardo, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Jon Bilbao, Diana Guallar, Miguel Fidalgo, Susana Bravo, Carlos Dieguez, Maria L. Martinez-Chantar, Oscar Millet, Jose M. Mato, Markus Schwaninger, Vincent Prevot, Javier Crespo, Gema Fruhbeck, Paul Iruzubieta, Ruben Nogueiras
Summary: O-GlcNAcylation is a post-translational modification that affects protein function and localization, and its deregulation is associated with various human diseases. This study reveals the role of O-GlcNAcylation in the progression of NAFLD, providing new avenues for therapeutic intervention.
MOLECULAR METABOLISM
(2023)
Review
Oncology
Pietro Guerra, Andrea Martini, Patrizia Pontisso, Paolo Angeli
Summary: Hepatocellular Carcinoma (HCC) is a common and aggressive cancer with limited treatment options. Immunotherapy has shown promising results in the treatment of human cancers, including HCC. However, the effectiveness of immunotherapy in HCC is limited, and the identification of new targets is crucial for improved outcomes.
Article
Chemistry, Medicinal
Monica Chinellato, Matteo Gasparotto, Santina Quarta, Mariagrazia Ruvoletto, Alessandra Biasiolo, Francesco Filippini, Luca Spiezia, Laura Cendron, Patrizia Pontisso
Summary: In recent years, studies on the inflammatory signaling pathways have identified new targets for novel therapies. This research reveals that the small molecule 1-PPA can bind to PAR2 and exhibit antagonistic effects on its activity, potentially providing a promising new approach for the treatment of PAR2-related diseases.
