Article
Biochemistry & Molecular Biology
Lukas Gola, Laura Bierhansl, Julia Csatari, Christina B. Schroeter, Lisanne Korn, Venu Narayanan, Manuela Cerina, Sara Abdolahi, Anna Speicher, Alexander M. Hermann, Simone Koenig, Albena T. Dinkova-Kostova, Tawfeeq Shekh-Ahmad, Sven G. Meuth, Heinz Wiendl, Ali Gorji, Matthias Pawlowski, Stjepana Kovac
Summary: Hyperexcitability is associated with neuronal dysfunction, cellular death, and neurodegeneration. NOX4, an NADPH oxidase, is found to regulate reactive oxygen species (ROS) levels and calcium homeostasis, thereby preventing hyperexcitability and neuronal death. These findings suggest that NOX4 might have a crucial role in neurodegenerative diseases by acting as a potential redox regulator.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Aleksandr E. Vendrov, Han Xiao, Andrey Lozhkin, Takayuki Hayami, Guomin Hu, Matthew J. Brody, Junichi Sadoshima, You-Yi Zhang, Marschall S. Runge, Nageswara R. Madamanchi
Summary: In acute sympathetic stress, catecholamine overload can induce stress cardiomyopathy. This study reveals that cardiomyocyte NOX4-dependent mitochondrial oxidative stress mediates inflammation and diastolic dysfunction in stress cardiomyopathy. Specifically, over-stimulation leads to the activation of resident macrophages and myocardial inflammation, resulting in fibrosis and impaired diastolic function.
Article
Biochemistry & Molecular Biology
Napissara Boonpraman, Sunmi Yoon, Chae Young Kim, Jong-Seok Moon, Sun Shin Yi
Summary: Oxidative stress and mitochondrial dysfunction play an important role in aging and neurodegenerative diseases, such as Parkinson's disease (PD). NOX4, a member of the NOX family, is associated with PD progression. In this study, we found that the hippocampus had elevated levels of NOX4 and α-synuclein during PD, and neuroinflammatory cytokines MPO and OPN were upregulated in astrocytes. Furthermore, upregulation of MPO and OPN induced mitochondrial dysfunction and ferroptosis in human astrocytes. Overall, our findings suggest that NOX4 cooperates with MPO and OPN to induce mitochondrial aberration in hippocampal astrocytes during PD.
Article
Biochemistry & Molecular Biology
Seong Ji Woo, Youngmi Kim, Harry Jung, Jae Jun Lee, Ji Young Hong
Summary: In this study, we found that miR-148a may protect against tuberculous pleural fibrosis by inhibiting the expression of NOX4 and POLDIP2, and reducing fibrogenesis and epithelial mesenchymal transition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Flavia Rezende, Pedro Felipe Malacarne, Niklas Mueller, Birgit Rathkolb, Martin Hrabe de Angelis, Katrin Schroeder, Ralf P. Brandes
Summary: The study found that Nox4 knockout mice exhibited similar weight loss and sodium sparing function under a low sodium diet, but showed reduced systolic blood pressure, heart-rate ratio, and heart to body weight ratio compared to wild-type mice, indicating that Nox4 plays a role in blood pressure regulation induced by low sodium diets.
Article
Pharmacology & Pharmacy
Trenton E. Banks, Maheshinie Rajapaksha, Li-Hui Zhang, Feng Bai, Ning-Ping Wang, Zhi-Qing Zhao
Summary: This study found that stabilizing GLP-1 levels can reduce Ang II-induced cardiac fibrosis and high blood pressure by inhibiting NOX4 expression and preserving mitochondrial integrity.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Yawei Bi, Xiao Lei, Ningli Chai, Enqiang Linghu
Summary: NOX4 is upregulated in pancreatic cancer and primarily produces hydrogen peroxide, exhibiting different properties from other NOX family subtypes. Recent studies suggest that NOX4 promotes pancreatic cancer occurrence and development, making it a potential therapeutic target in pancreatic cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Hui Zheng, Nannan Xu, Zihao Zhang, Fen Wang, Jie Xiao, Xiaoping Ji
Summary: This study found that GKT137831 can alleviate DOX-induced cardiomyocyte apoptosis by inhibiting NOX1/4-driven ROS production. The upregulation of the MAPK pathway induced by NOX1/4-derived ROS production may be the potential mechanism of GKT137831 action. GKT137831 may be a potential drug candidate to ameliorate DOX-induced cardiotoxicity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yi-Fan Huang, Guan Wang, Lu Ding, Zi-Ran Bai, Yi Leng, Jun-Wei Tian, Jian-Zeng Zhang, Yan-Qi Li, Yuan-Hua Qin, Xia Li, Xin Qi
Summary: Increasing evidence suggests that metabolic factors are involved in the pathological process of osteoarthritis (OA). This study confirms the elevated levels of lactate in OA patients and its correlation with other metabolic markers. Lactate can up-regulate specific receptors and activate signaling pathways leading to oxidative stress and chondrocyte damage.
Article
Biochemistry & Molecular Biology
M. Herranz-Iturbide, J. Lopez-Luque, E. Gonzalez-Sanchez, D. Caballero-Diaz, E. Crosas-Molist, B. Martin-Mur, M. Gut, A. Esteve-Codina, V Jaquet, J. X. Jiang, N. J. Torok, I Fabregat
Summary: NOX4 plays a role in promoting hepatocyte proliferation and repair during liver regeneration, with its deletion leading to accelerated liver recovery. NOX4-deleted mice show faster cell proliferation and better liver weight restoration, suggesting the potential of NOX4 as a therapeutic target for improving liver regeneration.
Article
Biochemistry & Molecular Biology
Anja Hofmann, Frieda Frank, Steffen Wolk, Albert Busch, Anna Klimova, Pamela Sabarstinski, Michael Gerlach, Dmitry Egorov, Irakli Kopaliani, Sonke Weinert, Bianca Hamann, David M. Poitz, Coy Brunssen, Henning Morawietz, Katrin Schroder, Christian Reeps
Summary: The study found that low NOX4 mRNA expression is associated with an increased risk for symptomatic carotid artery stenosis and reduced plaque stabilizing mechanisms, suggesting protective effects of NOX4 in human advanced atherosclerosis.
Article
Pharmacology & Pharmacy
Hongxiang Jiang, Fei Li, Linzhi Cai, Qianxue Chen
Summary: NOX4 plays a role in angiogenesis in glioblastoma through ROS production, and TSPO is an upstream target of NOX4-derived mitochondrial ROS. The TSPO-NOX4 signaling pathway could serve as a potential molecular target for therapeutic strategies in glioblastoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ildiko Szanto
Summary: Cancer cells can adapt to hypoxic environments through metabolic rewiring and synthesis of antioxidant molecules. NOX4, a member of the NOX family enzymes, plays a key role in the oncogenic metabolic adaptation of cancer cells by regulating diverse metabolic processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Shun Hay Pun, Karla M. O'Neill, Kevin S. Edgar, Eleanor K. Gill, Arya Moez, Hojjat Naderi-Meshkin, Sudhir B. Malla, Michelle B. Hookham, Mohammed Alsaggaf, Vinuthna Vani Madishetti, Bianca Botezatu, William King, Coy Brunssen, Henning Morawietz, Philip D. Dunne, Derek P. Brazil, Reinhold J. Medina, Chris J. Watson, David J. Grieve
Summary: This study aimed to investigate and define the contribution of NOX4 NADPH oxidase to hypoxia-induced dysfunction and explore its potential as a therapeutic target. The results showed that activation of the PLAC8-NOX4 signaling axis improved the angiogenic functions of CB-ECFCs under hypoxic conditions.
Review
Biochemistry & Molecular Biology
Renu A. Kowluru
Summary: Diabetic retinopathy, a leading cause of vision loss in working-age adults, involves oxidative stress and the activation of Nox2 and Rac1, with inhibitors of these enzymes potentially serving as therapeutic interventions.