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
Cell Biology
Hyungsu Kim, Sunhong Moon, Dohyung Lee, Jinhong Park, Chang-Hee Kim, Young-Myeong Kim, Yoon Kyung Choi
Summary: Korean red ginseng extract (KRGE) increases the mitochondrial functions of astrocytes by inducing the expression of SIRT3, leading to increased oxygen consumption and mitochondrial membrane potential. This activation of SIRT3 stabilizes HIF-1a levels in an ERRa-independent manner through the Tom22-HIF-1a pathway.
Article
Biochemistry & Molecular Biology
Corry D. Bondi, Brittney M. Rush, Hannah L. Hartman, Jiaxuan Wang, Mohammad M. Al-Bataineh, Rebecca P. Hughey, Roderick J. Tan
Summary: Acute kidney injury (AKI) is a rapid decline in renal function that can occur after ischemia/reperfusion injury (IRI). Severe IRI reduces NRF2 activity, while mild IRI increases NRF2 activity and aids in renal recovery. We found that hypoxia-inducible factor-1 alpha (HIF-1 alpha) mediates NRF2 activity, and severe ischemic AKI suppresses NRF2 through HIF-1 alpha, leading to disease progression.
Article
Integrative & Complementary Medicine
Ting Wang, Pinghan Wang, Song Wang, Yu Ma, Ziqiao Zhao, Fangyi Long
Summary: Radiotherapy plays a crucial role in breast cancer treatment, but radioresistance limits its effectiveness. This study found that Wogonin can reverse radioresistance in breast cancer by inhibiting the Nrf2/HIF-1α pathway and inducing apoptosis, offering potential strategies to overcome the limitations of current radiotherapy.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2023)
Article
Cell Biology
Xin Jin, Liansheng Gong, Ying Peng, Le Li, Gang Liu
Summary: In the hypoxic tumor microenvironment, Nrf2 regulates HIF-1 alpha to promote cisplatin resistance in HepG2/DDP cells, indicating a potential mechanism for chemotherapy resistance in vivo.
Article
Medicine, Research & Experimental
Zhi Zhang, Huiqing Wen, Bangjian Peng, Jun Weng, Fanhong Zeng
Summary: This study reveals that high-fat diet leads to the development of fatty liver in obese mice, with TRAF6 mediating ubiquitination of EZH2 to increase miR-429 expression that targets PPARa. TRAF6 promotes cholesterol accumulation in liver cells through the EZH2/miR-429/PPARa axis.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Multidisciplinary Sciences
Ian R. R. Phillips, Sunil Veeravalli, Sanjay Khadayate, Elizabeth A. A. Shephard
Summary: This study reveals that disruption of Fmo5 gene leads to alteration in metabolites and gene expression in the liver of mice, resulting in a lean phenotype. FMO5 is involved in regulating oxidative stress response, unfolded protein response, and adaptation to metabolic stress. It also plays a role in lipid homeostasis, glucose metabolism, cytosolic NADPH generation, and one-carbon metabolism. The findings provide important insights into the function and regulatory pathways of FMO5.
Article
Cell Biology
Xiao Yang, Yanshuang Zhang, Keyi Geng, Ke Yang, Jiaxiang Shao, Weiliang Xia
Summary: Sirt3 plays a protective role in ischemic stroke by regulating VEGF expression, protecting neuronal cells and the blood-brain barrier, and combating inflammatory responses.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Arno R. Bourgonje, Damian Kloska, Anna Grochot-Przeczek, Martin Feelisch, Antonio Cuadrado, Harry van Goor
Summary: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are closely associated with inflammation and overproduction of reactive oxygen species (ROS). The variability in disease activity and response to therapy poses challenges to diagnosis and patient care. The use of redox metabolomics approaches and integration of clinical-omics can help identify disrupted redox signaling pathways and develop personalized redox medicine approaches for IBD treatment.
Article
Biochemistry & Molecular Biology
Jacopo Di Gregorio, Lucia Cilenti, Camilla T. Ambivero, Thomas Andl, Ronglih Liao, Antonis S. Zervos, Jacopo Di Gregorio
Summary: UBXN7 is a cofactor protein that regulates the protein levels of NRF2 and HIF-1α, and coordinates the activity of CRL3(KEAP1) and CRL2(VHL) ubiquitin ligase complexes under conditions of oxidative stress or hypoxia. This regulation leads to different metabolic states and adaptive responses to mitochondrial stress.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Review
Health Care Sciences & Services
Eduardo Salido, David J. Timson, Isabel Betancor-Fernandez, Rogelio Palomino-Morales, Ernesto Anoz-Carbonell, Juan Luis Pacheco-Garcia, Milagros Medina, Angel L. Pey
Summary: This article reviews the importance of the interaction between HIF-1 alpha and NQO1 in anticancer therapy. Targeting the stability and/or function of NQO1 can lead to the destabilization of HIF-1 alpha, which has potential therapeutic implications. The article also discusses the molecular interactions of NQO1 with various proteins, including cancer-associated factors. By targeting its chaperone NQO1, novel anticancer therapies may be developed.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Multidisciplinary Sciences
Peng Wang, Ming Ni, Yizhu Tian, Hao Wang, Jiannan Qiu, Wenhua You, Song Wei, Yong Shi, Jinren Zhou, Feng Cheng, Jianhua Rao, Ling Lu
Summary: The study demonstrated decreased expression of Nrf2 in NASH liver macrophages. Nrf2 deficiency exacerbated liver steatosis and inflammation in high-fat diet-fed mice. By modulating YAP-mediated NLRP3 inflammasome activity, macrophage Nrf2 slows down the progression of NASH.
Article
Biochemistry & Molecular Biology
Bo Huang, Jie Ding, Hongrong Guo, Hongjuan Wang, Jianqun Xu, Quan Zheng, Lijun Zhou
Summary: SIRT3 affects the development of lung cancer under hypoxic conditions by regulating the ROS-FPR1/HIF-1 alpha axis. SIRT3 overexpression inhibits cell proliferation, invasion, and migration, and decreases inflammation levels. In addition, SIRT3 expression is down-regulated, while FPR1 and HIF-1 alpha expression are up-regulated under hypoxic conditions.
CELL BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Matthew J. Smith, Fan Yang, Alexander Griffiths, Alexander Morrell, Sarah J. Chapple, Richard C. M. Siow, Theodora Stewart, Wolfgang Maret, Giovanni E. Mann
Summary: Zinc is vital for cellular antioxidant defenses and imbalanced zinc homeostasis increases the risk of coronary heart disease and ischemia/reperfusion injury. In human coronary artery cells, the total intracellular zinc content decreases significantly when oxygen levels are lowered. This is accompanied by differences in redox phenotype and metal profiles, indicating the involvement of NRF2 signaling in zinc regulation.
Article
Biochemistry & Molecular Biology
Zixuan Wang, Chunchun Zhu, Yangyang Song, Xiaoyun Chen, Jie Zheng, Lian He, Xing Liu, Zhu Chen
Summary: This study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells.
Article
Cell Biology
Marta Montori-Grau, David Aguilar-Recarte, Mohammad Zarei, Javier Pizarro-Delgado, Xavier Palomer, Manuel Vazquez-Carrera
Summary: This study found that endoplasmic reticulum (ER) stress downregulates the expression of PGC-1 alpha in skeletal muscle through the activation of ATF4 and the mTOR-CRTC2 pathway. These findings suggest that inhibition of ATF4 and the mTOR-CRTC2 axis could be a therapeutic target for insulin resistant states.
CELL COMMUNICATION AND SIGNALING
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Rosalia Rodriguez-Rodriguez, Sabina Quader
Review
Nutrition & Dietetics
Carmen M. Claro-Cala, Francesc Jimenez-Altayo, Sebastian Zagmutt, Rosalia Rodriguez-Rodriguez
Summary: Dietary components, specifically olive oil triterpenes, have potential protective effects against obesity and related metabolic and cardiovascular disorders. This review focuses on understanding the molecular mechanisms and targets of these triterpenic compounds in improving glucose and insulin homeostasis, lipid metabolism, adiposity, and cardiovascular dysfunction in obesity. The study highlights the potential of olive oil as a dietary component for long-term management of obesity and metabolic syndrome in humans.
Article
Biochemistry & Molecular Biology
Jose Fernando Rinaldi de Alvarenga, Mar Garcia-Aloy, Marynka Ulaszewska, Sebastian Zagmutt, Marta Perez-Montero, Urska Vrhovsek, Rosa M. Lamuela-Raventos, Rosalia Rodriguez-Rodriguez
Summary: This study investigates the impact of sofrito, a tomato and olive oil-based sauce, on energy metabolism in obese rats. The results show that sofrito intake promotes lipid oxidation, ketogenesis activation, and alters the lipidomic profile in fat depots. These findings provide further evidence for the beneficial effects of sofrito and components of the Mediterranean diet against obesity.
Article
Biochemistry & Molecular Biology
Anna Fosch, Maria Rodriguez-Garcia, Cristina Miralpeix, Sebastian Zagmutt, Maite Larranaga, Ana Cristina Reguera, Jesus Garcia-Chica, Laura Herrero, Dolors Serra, Nuria Casals, Rosalia Rodriguez-Rodriguez
Summary: Sensing of long-chain fatty acids (LCFA) in the hypothalamus modulates energy balance and disruption leads to obesity. The effects of saturated or unsaturated LCFA on hypothalamic-brown adipose tissue (BAT) axis and underlying mechanisms were investigated. Unsaturated LCFA increased BAT thermogenesis through CPT1C-mediated FA metabolism shift, while saturated LCFA did not. These findings provide new insight into neuronal circuitries activated by LCFA to drive thermogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Rosalia Rodriguez-Rodriguez, Anna Fosch, Jesus Garcia-Chica, Sebastian Zagmutt, Nuria Casals
Summary: Tackling obesity requires uncovering new molecular pathways. The brain, especially the hypothalamus, plays a major role in regulating metabolic signals that control feeding behavior and energy expenditure. Hypothalamic lipid metabolism, particularly the CPT1 isoforms, are potential targets for obesity treatment.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
David Aguilar-Recarte, Emma Barroso, Meijian Zhang, Patricia Rada, Javier Pizarro -Delgado, Lucia Pena, Xavier Palomer, Angela M. Valverde, Walter Wahli, Manuel Vazquez-Carrera
Summary: This study reveals a novel mechanism by which the activation of AMPK by metformin is dependent on the upregulation of GDF15, independent of the central nervous system. This finding provides insights into the therapeutic effects of metformin in the treatment of type 2 diabetes.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Cell Biology
Rut Fado, Sebastian Zagmutt, Laura Herrero, Helena Muley, Rosalia Rodriguez-Rodriguez, Huichang Bi, Dolors Serra, Nuria Casals
Summary: There is a need for reliable genetic biomarkers in the diagnosis, prognosis, and treatment of different tumor types. One potential biomarker is CPT1C, a neuronal protein involved in cancer cell adaptation to nutrient depletion and hypoxia. However, its molecular role in cancer cells is controversial. This review discusses the evidence on CPT1C in neurons and its potential role in lipid metabolism and cell adaptation to stressors in cancer cells.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Meijian Zhang, Emma Barroso, Maria Ruart, Lucia Pena, Mona Peyman, David Aguilar-Recarte, Marta Montori-Grau, Patricia Rada, Clara Cugat, Carla Montironi, Mohammad Zarei, Javier Jurado-Aguilar, Antoni Camins, Jesus Balsinde, Angela M. Valverde, Walter Wahli, Xavier Palomer, Manuel Vazquez-Carrera
Summary: Elafibranor has been found to ameliorate steatosis, inflammation, and fibrogenesis in the livers of mice fed a high-fat diet. Unexpectedly, Elafibranor also increases the levels of the EMT-promoting protein S100A4 through PPAR β/δ activation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Meijian Zhang, Andrea Bagan, Donna Martinez, Emma Barroso, Xavier Palomer, Santiago Vazquez, Carmen Escolano, Manuel Vazquez-Carrera
Summary: A novel series of AMPK activators were designed, synthesized, and evaluated in vitro to upregulate GDF15 levels as a strategy for treating obesity and type 2 diabetes mellitus. Compound 21 showed a higher increase in GDF15 mRNA levels and protein levels compared with metformin and BC1618 in human hepatic cells.
Review
Pharmacology & Pharmacy
Emma Barroso, Marta Montori-Grau, Walter Wahli, Xavier Palomer, Manuel Vazquez-Carrera
Summary: Metformin, the most prescribed drug for T2DM, has both liver and gut as important targets for its glucose-lowering effect through new mechanisms of action. The understanding of metformin's action in these organs and its relevance in patients remains a challenge for current and future research, potentially impacting T2DM drug development.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Materials Science, Biomaterials
Jesus Garcia-Chica, West Kristian Dizon Paraiso, Sebastian Zagmutt, Anna Fosch, Ana Cristina Reguera, Sara Alzina, Laura Sanchez-Garcia, Shigeto Fukushima, Kazuko Toh, Nuria Casals, Dolors Serra, Laura Herrero, Jordi Garcia, Kazunori Kataoka, Xavier Ariza, Sabina Quader, Rosalia Rodriguez-Rodriguez
Summary: Targeting brain lipid metabolism is a promising strategy for regulating energy balance and combating metabolic diseases. However, it is difficult to selectively deliver drugs to the hypothalamus, which plays a crucial role in controlling metabolism. This study proposes the use of a nanomedicine that can effectively deliver a CPT1A inhibitor to the hypothalamus, leading to the modulation of food intake and peripheral metabolism in mice.
BIOMATERIALS SCIENCE
(2023)
Article
Medicine, Research & Experimental
Mona Peyman, Emma Barroso, Andreea L. Turcu, Francesc Estrany Jr, Daire Smith, Javier Jurado-Aguilar, Patricia Rada, Christophe Morisseau, Bruce D. Hammock, Angela M. Valverde, Xavier Palomer, Carles Galdeano, Santiago Vazquez, Manuel Vazquez-Carrera
Summary: This study demonstrates that targeting sEH with degraders can degrade the protein, regulate AMPK activation, and reduce ER stress and inflammation in mice.
BIOMEDICINE & PHARMACOTHERAPY
(2023)