Article
Pharmacology & Pharmacy
Levon M. Khachigian
Summary: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. The zinc finger transcription factor Egr-1 plays a key role in regulating various pro-inflammatory processes underlying CVD. This article reviews recent progress in understanding the MEK-ERK-Egr-1 cascade and its regulation by factors and agents, offering new opportunities for therapeutic intervention in CVD.
VASCULAR PHARMACOLOGY
(2023)
Article
Oncology
Sara J. Hamis, Yury Kapelyukh, Aileen McLaren, Colin J. Henderson, C. Roland Wolf, Mark A. J. Chaplain
Summary: The study developed a mechanistic mathematical model to describe the synergistic action of dabrafenib and trametinib on ERK activity in BRAFV600E-mutant melanoma cells, elucidating the molecular mechanism underlying vertical inhibition of the BRAF-MEK-ERK cascade.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Hannah Mason, Ganesha Rai, Arina Kozyr, Nathaniel De Jonge, Emily Gliniewicz, Lars J. Berg, Gal Wald, Cayce Dorrier, Mark J. Henderson, Alexey Zakharov, Tristan Dyson, John Audley, Anthony M. Pettinato, Elias Carvalho Padilha, Pranav Shah, Xin Xu, Thomas L. Leto, Anton Simeonov, Kol A. Zarember, Dorian B. McGavern, John I. Gallin
Summary: NADPH oxidases (NOX's) and the reactive oxygen species (ROS) they produce are involved in various physiological processes, but excessive ROS production is associated with several diseases. In this study, a small molecule inhibitor, NCATS-SM7270, was developed and shown to specifically inhibit NOX2 activity in human and mouse granulocytes. The role of different NOX isoforms in mild traumatic brain injury (mTBI) was investigated, and it was found that NOX2 deficiency provided protection against mTBI pathology, while NOX4 deficiency exacerbated the injury. Treatment of mice with NCATS-SM7270 after mTBI reduced cortical cell death in a dose-dependent manner, and also partially reversed cortical damage in NOX4-deficient mice. These findings highlight the potential of NCATS-SM7270 as a specific inhibitor of NOX2 in protecting against NOX2-dependent cell death in mTBI.
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
Biochemistry & Molecular Biology
Simona-Adriana Manea, Mihaela-Loredana Vlad, Alexandra-Gela Lazar, Horia Muresian, Maya Simionescu, Adrian Manea
Summary: Dysregulated epigenetic mechanisms, specifically LSD1/KDM1A, play a crucial role in atherosclerosis by promoting oxidative stress and inflammation. Inhibition of LSD1 effectively reduces the extent of atherosclerotic lesions and decreases markers of immune cell infiltration and vascular inflammation, making it a potential therapeutic target.
Review
Biochemistry & Molecular Biology
Jie Fang, Rui Sheng, Zheng-Hong Qin
Summary: This review highlights the role of Nox-derived ROS in regulating various signals in the central nervous system, with different Nox homologues leading to different signaling cascades. The varied roles of NOX enzyme homologues in different signaling pathways and conditions underscore the need for selective Nox inhibitors in treating CNS diseases.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Cell Biology
Zhen-Zhen Liu, Wei Chen, Cheng-Kai Zhou, Ke Ma, Yu Gao, Yong-Jun Yang
Summary: This study revealed the importance of STING in promoting extracellular traps (ETs) formation through the ROS-ERK signaling pathway during Staphylococcus aureus infection. STING deficiency led to decreased cell-free DNA (cfDNA) level, reduced expression of citrullinated histone H3 (CitH3), and diminished DNA colocalization with CitH3 and myeloperoxidase (MPO). Additionally, STING(-/-) BMDMs exhibited increased levels of extracellular bacteria compared to WT BMDMs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yu. V. Filina, I. V. Tikhonova, A. G. Gabdoulkhakova, A. A. Rizvanov, V. G. Safronova
Summary: The study highlights the importance of FPR2 and its signaling pathways in understanding the activity of immune cells, particularly in the phosphorylation and activation of ERK1/2. The research also reveals the significant role of ROS in regulating ERK activity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Oncology
Antonella Catalano, Mojca Adlesic, Thorsten Kaltenbacher, Rhena F. U. Klar, Joachim Albers, Philipp Seidel, Laura P. Brandt, Tomas Hejhal, Philipp Busenhart, Niklas Roehner, Kyra Zodel, Kornelia Fritsch, Peter J. Wild, Justus Duyster, Ralph Fritsch, Tilman Brummer, Ian J. Frew
Summary: The study demonstrates that the combined use of MEK and ERK inhibitors can prevent the emergence of drug resistance, but may not be effective if cancer cells are resistant to single agents. Drug resistance involves complex rewiring of cellular kinase signaling networks, which are not overlapping between different cancer cell lines. The identification of new drug sensitivities in some resistant cells suggests potential additional therapeutic targets in oncogenic RAS-driven tumors.
Article
Biochemistry & Molecular Biology
Chuntian Huang, Ruijuan Du, Xuechao Jia, Kangdong Liu, Yan Qiao, Qiong Wu, Ning Yao, Lu Yang, Liting Zhou, Xuejiao Liu, Pu Xiang, Mingxia Xin, Yan Wang, Xiaojie Chen, Dong Joon Kim, Zigang Dong, Xiang Li
Summary: The study revealed that CDK15 plays a pivotal role in colorectal cancer progression by phosphorylating PAK4 to promote tumor growth. The CDK15-PAK4 axis may serve as a novel therapeutic target for colorectal cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Pui-Kei Wu, Seung-Keun Hong, Jong-In Park
Summary: The study found that RNA interference of mortalin can induce cell death in vemurafenib-resistant B-Raf mutant melanoma cells, and chemical inhibition of MEK1/2 and ERK1/2 can suppress mortalin depletion-induced death. Therefore, mortalin may serve as a potential therapeutic target for BRAFi-resistant BRAF mutant tumors.
Article
Endocrinology & Metabolism
Jeanesse Scerri, Christian Scerri, Felix Schaefer-Ruoff, Simon Fink, Markus Templin, Godfrey Grech
Summary: This study aims to differentiate between intrinsic and acquired trastuzumab resistance mechanisms in breast cancer cells by quantifying changes in protein expression and activity. The findings suggest novel resistance mechanisms and potential therapeutic combinations.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, Research & Experimental
Akira Ishimitsu, Akihiro Tojo, Hiroshi Satonaka, Toshihiko Ishimitsu
Summary: Tochu tea and geniposidic acid can suppress NADPH oxidase, increase eNOS activity, and improve blood pressure and renal hemodynamics.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Geriatrics & Gerontology
Seul Gi Kim, Jin Young Sung, Young Jin Kang, Hyoung Chul Choi
Summary: Reactive oxygen species (ROS) are a key risk factor of cellular senescence and age-related diseases, and protein kinase C (PKC) has been shown to activate NADPH oxidases (NOXs), which generate ROS. The correlation between PKC and senescence has not been reported in vascular smooth muscle cell (VSMC). Our study revealed that H2O2 decreased PTEN expression, increased PKC delta phosphorylation, upregulated NOX1 subunits, and induced VSMC senescence via p53-p21 signaling pathway. However, fisetin inhibited cellular senescence induced by the PTEN-PKC delta-NOX1-ROS signaling pathway, suggesting that downregulation of PKC delta by flavonoids provides a potential means of treating age-associated diseases.
ARCHIVES OF GERONTOLOGY AND GERIATRICS
(2023)
Article
Hematology
Craig B. Harrison, Silvia Cellone Trevelin, Daniel A. Richards, Celio X. C. Santos, Greta Sawyer, Andrea Markovinovic, Xiaohong Zhang, Min Zhang, Alison C. Brewer, Xiaoke Yin, Manuel Mayr, Ajay M. Shah
Summary: Fibroblast-specific deficiency of Nox2 attenuated ANG II-induced vascular remodeling and hypertension in mice, suggesting a crucial role for fibroblast Nox2 in regulating paracrine signaling to vascular smooth muscle cells via factors such as GDF6.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Elisabeth Deindl, Paul H. A. Quax
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Konda Kumaraswami, Natallia Salei, Sebastian Beck, Stephan Rambichler, Anna-Kristina Kluever, Manuel Lasch, Lisa Richter, Barbara U. Schraml, Elisabeth Deindl
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Manuel Lasch, Amelia Caballero Martinez, Konda Kumaraswami, Hellen Ishikawa-Ankerhold, Sarah Meister, Elisabeth Deindl
Editorial Material
Cell Biology
Elisabeth Deindl, Paul H. A. Quax
Article
Biochemistry & Molecular Biology
Matthias Kubler, Sebastian Beck, Silvia Fischer, Philipp Goetz, Konda Kumaraswami, Hellen Ishikawa-Ankerhold, Manuel Lasch, Elisabeth Deindl
Summary: The study shows that the absence of CIRP can improve angiogenesis and regeneration of ischemic muscle tissue, likely by influencing macrophage polarization towards regenerative M2-like macrophages.
Article
Biochemistry & Molecular Biology
Philipp Goetz, Anna Braumandl, Matthias Kuebler, Konda Kumaraswami, Hellen Ishikawa-Ankerhold, Manuel Lasch, Elisabeth Deindl
Summary: The study found that deficiency of complement factor C3 increases the accumulation of neutrophils and M2-like polarized macrophages in ischemic muscle tissue, thereby promoting angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Chien-Sin Chen, Jasmin Weber, Stephan Jonas Holtkamp, Louise Madeleine Ince, Alba de Juan, Chen Wang, Lydia Lutes, Coline Barnoud, Burak Kizil, Sophia Martina Hergenhan, Johanna Salvermoser, Manuel Lasch, Elisabeth Deindl, Barbara Schraml, Dirk Baumjohann, Christoph Scheiermann
Summary: Peripheral nerve injury can cause immune cell-mediated destruction of the affected nerve, leading to pro-inflammatory effect on lymph node function and expansion. This effect can be rescued by beta 2 adrenergic receptor agonists.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Chemistry, Multidisciplinary
Silvia Fischer, Elisabeth Deindl
Summary: Extracellular vesicles (EVs) are important for cell-to-cell communication by delivering various RNA, proteins, lipids, and nucleotides. Different types of EVs, including exosomes, cell surface-derived EVs, and apoptotic bodies, contain different RNA species and can be isolated, quantified, and characterized using specific methods.
APPLIED SCIENCES-BASEL
(2021)
Article
Biochemistry & Molecular Biology
Matthias Kuebler, Philipp Goetz, Anna Braumandl, Sebastian Beck, Hellen Ishikawa-Ankerhold, Elisabeth Deindl
Summary: The study demonstrates increased ischemia-induced angiogenic capacities in C57BL/6J mice compared to SV-129 mice, with the latter showing aggravated tissue damage, inflammation, and impaired angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Biochemistry & Molecular Biology
Elisabeth Deindl, Paul H. A. Quax
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Christoph Arnholdt, Konda Kumaraswami, Philipp Goetz, Matthias Kuebler, Manuel Lasch, Elisabeth Deindl
Summary: Gamma delta T cell depletion leads to increased accumulation of leukocytes and inflammatory macrophages, along with impaired angiogenesis.
Article
Biochemistry & Molecular Biology
Philipp Goetz, Sharon O. Azubuike-Osu, Anna Braumandl, Christoph Arnholdt, Matthias Kuebler, Lisa Richter, Manuel Lasch, Lisa Bobrowski, Klaus T. Preissner, Elisabeth Deindl
Summary: Injection of CVF can enhance arteriogenesis and improve perfusion recovery in a murine hind limb model. The study found that CVF injection increases the number of proliferating vascular cells, luminal diameter of collateral vessels, neutrophils, platelet-neutrophil aggregates, and mast cell activation in the perivascular space. Additionally, it leads to the polarization of pro-arteriogenic macrophages around growing collaterals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Silvia Fischer, Elisabeth Deindl
Article
Biochemistry & Molecular Biology
Konda Kumaraswami, Christoph Arnholdt, Elisabeth Deindl, Manuel Lasch
Summary: Increasing evidence suggests that lymphocytes play distinct roles in inflammation-induced tissue remodeling and tissue damage. Arteriogenesis describes the growth of natural bypasses from pre-existing collateral arteries. The role of innate immune cells is widely understood in the process of arteriogenesis, whereas the role of lymphocytes remains unclear and is the subject of the present study.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matthias Kuebler, Sebastian Beck, Lisa Lilian Peffenkoever, Philipp Goetz, Hellen Ishikawa-Ankerhold, Klaus T. Preissner, Silvia Fischer, Manuel Lasch, Elisabeth Deindl
Summary: Depletion of eCIRP in a mouse model of muscle ischemia resulted in increased angiogenesis, reduced leukocyte recruitment, and a shift in macrophage polarization towards a regenerative phenotype. These findings suggest that eCIRP plays a key role in modulating angiogenesis and leukocyte responses during muscle ischemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)