Article
Multidisciplinary Sciences
Zhihui Fong, Caoimhin S. Griffin, Roddy J. Large, Mark A. Hollywood, Keith D. Thornbury, Gerard P. Sergeant
Summary: P2X1 receptors are inhibited by EPAC activators, while P2X2 current amplitudes are enhanced. PKA activators have no effect on P2X1 receptors but inhibit P2X2 receptors. The inhibitory effects of EPAC on P2X1 receptors can be prevented through mutations and an inhibitor of Rac1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Muhammad Bilal Ahmed, Abdullah A. A. Alghamdi, Salman Ul Islam, Joon-Seok Lee, Young-Sup Lee
Summary: Cancer, one of the leading causes of death globally, remains unclear in its fundamental principles. Understanding the key signaling mechanisms that cause cancer cell malignancy may help uncover new pharmaco-targets. Targeting cAMP and its effectors, crucial for tumor growth and development, may serve as a useful cancer treatment strategy.
Article
Pharmacology & Pharmacy
Edward E. Putnins, Verena Goebeler, Mahyar Ostadkarampour
Summary: RG0216 significantly decreased LPS-induced IL-6 and IL-1 beta gene and protein expression in an epithelial cell culture model, with similar effectiveness to deprenyl. This reduction occurred downstream of the cAMP-PKA/EPAC signaling cascade, providing a novel mechanism by which MAO-B selective inhibitors regulate LPS-induced cytokine expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Cui Zhu, Li Wang, Xiaoyan Nie, Xuefen Yang, Kaiguo Gao, Zongyong Jiang
Summary: This study investigates the mechanism of dbcAMP on porcine fat deposition. The results suggest that dbcAMP regulates gene expression related to adipocyte differentiation and fat metabolism through the cAMP-PKA pathway, leading to reduced fat deposition.
ANIMAL BIOTECHNOLOGY
(2023)
Article
Cell Biology
Lu Gan, Qiyong Li, Jigang Pan, Li Chen
Summary: The proliferative potential of adult mammalian cardiomyocytes is inhibited by glucocorticoids, which target the cAMP-PKA-YAP signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Article
Neurosciences
Ahmed Maher, Nesrine El Sayed, Heba Nafea, Mohamed Gad
Summary: This study demonstrated that PDE4 inhibitors restore memory through a dual mechanism involving PKA and Epac pathways.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Victoria Markova, Leo Bogdanov, Elena Velikanova, Anastasia Kanonykina, Alexey Frolov, Daria Shishkova, Anastasia Lazebnaya, Anton Kutikhin
Summary: Current techniques for detecting vasa vasorum (VV) in vascular pathology have limitations in evaluating vascular geometry and clinical relevance. This study found that markers for smooth muscle cells, such as alpha-SMA and SM-MHC, provide better results irrespective of the primary antibody origin, fluorophore, or VV type. Furthermore, these markers allow unbiased evaluation of VV area under vasospasm. Identification of specific markers for arterial, venous, lymphatic, or capillary differentiation requires high-throughput searches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Zhenyu Guo, Tingqin Huang, Yingfei Liu, Chongxiao Liu
Summary: This study aimed to investigate the effect of Parathyroid hormone-related peptide (PTHrP) on glioblastoma stem cells (GSCs) and its potential as a therapeutic target for glioblastoma (GBM). The results showed that PTHrP promotes the proliferation of GSCs by activating the cAMP/PKA signaling pathway, suggesting its potential as a therapeutic target for GBM treatment.
INTERNATIONAL JOURNAL OF STEM CELLS
(2023)
Article
Pharmacology & Pharmacy
Fabio Alejandro Aguilar Mora, Nshunge Musheshe, Asmaa Oun, Manon Buist-Homan, Frank Lezoualc'h, Xiaodong Cheng, Martina Schmidt, Han Moshage
Summary: This study demonstrates that elevated cAMP levels protect against diclofenac-induced liver injury by preserving mitochondrial integrity through the EPAC pathway. The findings suggest that cAMP-EPAC may be a potential target for the treatment of DILI and liver injury involving mitochondrial dysfunction.
MOLECULAR PHARMACOLOGY
(2021)
Article
Cell Biology
Harm Maarsingh, Anouk Oldenburger, Bing Han, Annet B. Zuidhof, Carolina R. S. Elzinga, Wim Timens, Herman Meurs, Ramadan B. Sopi, Martina Schmidt
Summary: The expression of bronchodilatory beta(2)-adrenoceptors and bronchoconstrictive muscarinic M-3-receptors varies with the size of the airways. In COPD, beta(2)-agonists and muscarinic M-3-antagonists (anticholinergics) are commonly used as bronchodilators. Studies have shown that glycopyrrolate provides protection for both large and small airways, while the protective effect of indacaterol is dependent on the type of contractile stimulus in small airways. Additionally, in a guinea pig model, it was observed that the synergistic bronchoprotective effect of indacaterol and glycopyrrolate is enhanced in COPD.
Article
Medicine, Research & Experimental
Fabio Alejandro Aguilar Mora, Nshunge Musheshe, Johanna C. Arroyave Ospina, Yana Geng, Juan M. Soto, Jose A. Rodrigo, Tatiana Alieva, Manon Buist-Homan, Frank Lezoualc'h, Xiaodong Cheng, Martina Schmidt, Han Moshage
Summary: The study demonstrates that metformin protects against diclofenac (DF)-induced apoptosis in hepatocytes, with this protective effect being dependent on EPAC-2. Metformin is able to reverse the mitochondrial dysfunction induced by DF.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Endocrinology & Metabolism
Rachana Eshwaran, Matthias Kolibabka, Gernot Poschet, Gregor Jainta, Di Zhao, Loic Teuma, Katharina Murillo, Hans-Peter Hammes, Martina Schmidt, Thomas Wieland, Yuxi Feng
Summary: The study found that glucosamine may have a protective effect on diabetic retinopathy, but may cause damage to the blood vessels in the normal retina.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Nshunge Musheshe, Asmaa Oun, Angelica Maria Sabogal-Guaqueta, Marina Trombetta-Lima, Sarah C. Mitchel, Ahmed Adzemovic, Oliver Speek, Francesca Morra, Christina H. J. T. van der Veen, Frank Lezoualc'h, Xiaodong Cheng, Martina Schmidt, Amalia M. Dolga
Summary: By modulating the activity of Epac proteins in neuronal cells, the study showed that Epac1 inhibition can prevent cell death and loss of mitochondrial integrity induced by ferroptosis, while Epac2 inhibition has limited effects. This suggests that Epac1 may be a potential therapeutic target for preventing ferroptosis cell death associated with neurodegenerative diseases.
Article
Multidisciplinary Sciences
Xinhui Wu, I. Sophie T. Bos, Thomas M. Conlon, Meshal Ansari, Vicky Verschut, Luke van der Koog, Lars A. Verkleij, Angela D'Ambrosi, Aleksey Matveyenko, Herbert B. Schiller, Melanie Koenigshoff, Martina Schmidt, Loes E. M. Kistemaker, Ali Oender Yildirim, Reinoud Gosens
Summary: Currently, there is no pharmacological treatment targeting tissue repair in chronic disease. However, through a transcriptomics-guided drug target discovery strategy, researchers have identified potential drug targets expressed in alveolar epithelial progenitors, which have regenerative potential in restoring cigarette smoke-induced defects in both in vitro and in vivo experiments. Furthermore, they found that circadian clock and cell cycle/apoptosis signaling pathways were differentially expressed in alveolar epithelial progenitor cells in patients with chronic obstructive pulmonary disease (COPD), which was prevented by specific prostaglandin E2 or prostacyclin mimetics. The results suggest that specific targeting of EP and IP receptors could be therapeutic for tissue repair in COPD.
Article
Biochemical Research Methods
Hoeke A. Baarsma, Christina H. T. J. Van der Veen, Danique Lobee, Nienke Mones, Emily Oosterhout, Isabella Cattani-Cavalieri, Martina Schmidt
Summary: Cigarette smoke and air pollutants can cause pathological changes in bronchial epithelial cells, leading to lung function decline. Previous studies have shown that cigarette smoke exposure activates the release and signaling of TGF-beta 1, and reduces the expression of E-cadherin in 2D cell cultures. This study cultured bronchial epithelial cells in a 3D environment and found that cigarette smoke and air pollutants induce an epithelial-to-mesenchymal transition phenotype.
Article
Environmental Sciences
Xinhui Wu, Chiara Ciminieri, I. Sophie T. Bos, Manon E. Woest, Angela D'Ambrosi, Rene Wardenaar, Diana C. J. Spierings, Melanie Konigshoff, Martina Schmidt, Loes E. M. Kistemaker, Reinoud Gosens
Summary: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease caused by environmental pollution, particularly motor vehicle emissions. Diesel exhaust particles (DEP) exposure affects the epithelial-mesenchymal signaling niche in the distal lung, impairing tissue repair. Targeting oxidative stress and the WNT/β-catenin signaling pathway may be a potential strategy for restoring tissue repair in COPD.
ENVIRONMENTAL POLLUTION
(2022)
Article
Biochemistry & Molecular Biology
Ivana Cavallin, Marek Bartosovic, Tomas Skalicky, Praveenkumar Rengaraj, Martin Demko, Martina Christina Schmidt-Dengler, Aleksej Drino, Mark Helm, Stepanka Vanacova
Summary: This study analyzed the RNA targets of ALKBH8 and found that ALKBH8 not only binds to a known set of tRNAs containing wobble U, but also to several other types of noncoding RNAs.
Article
Biochemistry & Molecular Biology
Camila Oliveira da Silva, Jeane de Souza Nogueira, Adriana Paulino do Nascimento, Tatiana Victoni, Thiago Prudente Bartholo, Claudia Henrique da Costa, Andrea Monte Alto Costa, Samuel dos Santos Valenca, Martina Schmidt, Luis Cristovao Porto
Summary: COPD is a major contributor to morbidity and mortality worldwide, characterized by airflow limitation and diverse clinical features. The study identified genetic changes associated with COPD phenotypes and severity, as well as a higher prevalence of M2 markers. The findings have implications for future treatments and personalized therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Tong Zhang, Minh D. A. Luu, Amalia M. M. Dolga, Ulrich L. M. Eisel, Martina Schmidt
Summary: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders worldwide, impacting millions of people's life expectancy and quality. Recent research suggests overlapping mechanisms may underlie AD and PD, with novel cell death mechanisms, such as parthanatos, netosis, lysosome-dependent cell death, senescence, and ferroptosis, being modulated by cAMP signaling via PKA and Epac. This review focuses on the overlapping mechanisms between AD and PD, specifically in relation to cAMP signaling and the pharmacology of cAMP signaling pathways.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Clara Barbosa-de-Oliveira, Paolo Oliveira-Melo, Marcos Henrique Goncalves da Silva, Flavio Santos da Silva, Felipe Andrade Carvalho da Silva, Bruno Vinicios Silva de Araujo, Moacir Franco de Oliveira, Aristides Tadeu Correia, Sidnei Miyoshi Sakamoto, Samuel Santos Valenca, Manuella Lanzetti, Martina Schmidt, Emanuel Kennedy-Feitosa
Summary: This study investigates the role of eugenol (EUG) in cigarette smoke-induced acute lung injury (ALI) and how it modulates macrophage activity. The results show that EUG reduces inflammatory response and oxidative stress markers in vivo, and balances oxidative stress and cytokine release in vitro, indicating that it acts as a modulator of macrophage activity.
Article
Medicine, Research & Experimental
Johanna C. Arroyave-Ospina, Manon Buist-Homan, Martina Schmidt, Han Moshage
Summary: This study found that caffeine can protect liver cells from the toxic effects of fatty acids by modulating adenosine receptor signaling. By activating protein kinase A and inhibiting the A1AR receptor, caffeine can reduce lipid accumulation and harmful substances produced by mitochondria, thereby alleviating metabolic dysfunction-associated liver disease.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Tong Zhang, Nshunge Musheshe, Christina H. J. T. M. van der Veen, Helmut W. Kessels, Amalia Dolga, Peter De Deyn, Ulrich Eisel, Martina Schmidt
Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) and hyperphosphorylated tau in the brain. Recent studies have shown that memory retrieval is impaired in the early stage of AD. This study aimed to investigate the expression of proteins associated with Epac2-mediated memory in hippocampal postmortem samples of AD patients and experimental AD model mice.
Proceedings Paper
Engineering, Biomedical
Juan M. Soto, Fabio A. Aguilar Mora, Jose A. Rodrigo, Yana Geng, Nshunge Musheshe, Manon Buist-Homan, Frank Lezoualc'h, Xiaodong Cheng, Martina Schmidt, Han Moshage, Tatiana Alieva
Summary: Refractive index tomography compatible with conventional microscope is used to analyze primary rat hepatocyte injury induced by pharmacological treatments, revealing a correlation between mitochondrial malfunctioning and refractive index variations.
ADVANCES IN MICROSCOPIC IMAGING III
(2021)