Article
Physiology
Malte Verheyen, Michelle Puschkarow, Stefanie Gnipp, Doris Koesling, Marcus Peters, Evanthia Mergia
Summary: In this study, we investigated the role of NO-GC isoforms in respiration by measuring lung function parameters of isoform-specific knockout mice. Our findings suggest that NO-GC1-derived cGMP plays a significant role in regulating airway tone, while NO-GC2 affects tissue elasticity and airway reactivity.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Joseph C. Galley, Megan P. Miller, Subramaniam Sanker, Mingjun Liu, Iraida Sharina, Emil Martin, Delphine Gomez, Adam C. Straub
Summary: This study identifies Forkhead box subclass O protein 4 (FoxO4) as a key transcriptional regulator of GUCY1B3 expression, coding for sGC13 protein in human and animal smooth muscle cells (SMCs). This discovery may have important implications for future antihypertensive and vasodilatory therapies targeting NO production, sGC, or FoxO transcription factors.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Iraida Sharina, Karina Lezgyieva, Yekaterina Krutsenko, Emil Martin
Summary: This study characterized a rare sGC variant with reduced cGMP-forming activity, high susceptibility to oxidative stress, and diminished protein stability. These deficiencies contribute to the severity of moyamoya disease and achalasia symptoms in carriers of this variant.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Gang Wu, Iraida Sharina, Emil Martin
Summary: Nitric oxide (NO), carbon monoxide (CO), oxygen (O-2), and hydrogen sulfide (H2S) are gaseous molecules that play important roles in the physiology and pathophysiology of eukaryotes. Soluble guanylyl cyclase (sGC), a hemoprotein, acts as a sensor and transducer for these gases, as well as a transporter.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yuksel Korkmaz, Behrus Puladi, Kerstin Galler, Peer W. Kaemmerer, Agnes Schroeder, Lina Goelz, Tim Sparwasser, Wilhelm Bloch, Andreas Friebe, James Deschner
Summary: This study confirmed a decreased expression of sGC alpha(1)- and beta(1)-subunits in cementoclasts under inflammatory conditions, which may lead to increased cementum resorption. Therefore, pharmacological activation of sGC in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Cheng Zhong, Minze Xu, Senguel Boral, Holger Summer, Falk-Bach Lichtenberger, Cem Erdogan, Maik Gollasch, Stefan Golz, Pontus B. Persson, Johanna Schleifenbaum, Andreas Patzak, Pratik H. Khedkar
Summary: Aging affects the downstream signaling of the endothelial nitric oxide system in vascular smooth muscle, leading to compromised vasorelaxation even in the absence of histopathological alterations. The reduced expression of sGC and PDE5 may contribute to the impaired vasorelaxation in aged vessels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yue Dai, Emily M. Faul, Arnab Ghosh, Dennis J. Stuehr
Summary: Nitric oxide (NO) signaling in biology relies on its activating cyclic guanosine monophosphate (cGMP) production by the NO receptor soluble guanylyl cyclase (sGC). Physiological levels of NO trigger the mobilization of heme to immature sGC, leading to the construction of functional sGC heterodimers and increased active sGC levels. The process involves glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-heme complexes and the chaperone hsp90.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Maryam Alapa, Chuanlong Cui, Ping Shu, Hong Li, Vlad Kholodovych, Annie Beuve
Summary: The study found that redox modifications play a crucial role in NO activation of GC1, with NO-stimulated GC1 containing more bound Cys, potentially disulfide bonds. Mass spectrometry identified ten oxidized and two reduced Cys in NO-stimulated GC1, and computational modeling narrowed down potential Cys candidates involved in disulfide bonds to Cys489 and Cys571. Mutational studies confirmed the involvement of Cys489 and Cys571 in GC1's response to NO, potentially as a thiol/disulfide switch.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yueksel Korkmaz, Markus Plomann, Behrus Puladi, Ayseguel Demirbas, Wilhelm Bloch, James Deschner
Summary: The binding of nitric oxide to heme in the beta(1) subunit of soluble guanylyl cyclase activates the enzyme and increases cGMP production. Exogenous NO can inhibit mast cell degranulation via NO-cGMP signaling. However, oxidative or nitrosative stress can make the enzyme insensitive to NO. The study investigates the presence of mast cells and the expression of the alpha(1) and beta(1) subunits of soluble guanylyl cyclase in healthy and inflamed dental pulp.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Hari Prasad, John Kandam Kulathu Mathew, Sandhya S. Visweswariah
Summary: This review highlights the importance of Receptor Guanylyl Cyclase C (GC-C) in regulating intestinal fluid and ion homeostasis, and its causal link to intestinal inflammation, dysbiosis, and tumorigenesis. The GC-C signaling pathway plays a role in extra gastrointestinal functions such as appetite control, energy expenditure, visceral nociception, and behavioral processes. Recent research has also uncovered the involvement of GC-C in the ion-microbiome-immune axis in inflammatory bowel disease and suggests potential therapeutic strategies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Adam C. Straub, Annie Beuve
Summary: sGC is the main receptor for NO, catalyzing the production of cGMP to induce vasorelaxation and inhibit leukocyte and platelet aggregation. Enhancing cGMP levels or inhibiting cGMP breakdown can be used for the treatment of cardiovascular and pulmonary diseases.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2021)
Article
Cell Biology
Ayako Tonoki, Saki Nagai, Zhihua Yu, Tong Yue, Sizhe Lyu, Xue Hou, Kotomi Onuki, Kaho Yabana, Hiroki Takahashi, Motoyuki Itoh
Summary: This study identified the gyc beta gene as a negative regulator of age-related memory impairment (AMI) in fruit flies. It was shown that inhibition of the NO-sGC pathway enhanced intermediate-term memory (ITM) in aged individuals, suggesting a potential mechanism underlying memory impairment in aging.
Review
Multidisciplinary Sciences
Se-Min Kim, Tony Yuen, Jameel Iqbal, Mishaela R. Rubin, Mone Zaidi
Summary: The NO-cGMP-PKG pathway is crucial for skeletal homeostasis, but long-term use of NO is limited by off-target effects. Inhibiting cGMP-specific phosphodiesterase to promote the anabolic signal offers a potential treatment for osteoporosis with PDE5A inhibitors. Further research is needed to investigate the specific effects of PDE5A inhibition on bone cells and the pathophysiological changes in skeletal PDE5A expression.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Editorial Material
Microbiology
James M. Fleckenstein, Jacob P. Bitoun
Summary: The study shows how bats have evolutionarily maintained fluid homeostasis signaling while avoiding the pathogenic effects of ST.
CELL HOST & MICROBE
(2021)
Article
Biochemistry & Molecular Biology
Chien-Wei Chen, Luen-Kui Chen, Tai-Ying Huang, De-Ming Yang, Shui-Yu Liu, Pei-Jiun Tsai, Tien-Hua Chen, Heng-Fu Lin, Chi-Chang Juan
Summary: Plasma and tissue zinc ion levels are associated with obesity development. NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Tobias Haase, Robert Klopfleisch, Annalena Krost, Tilman Sauter, Karl Kratz, Jan Peter, Friedrich Jung, Andreas Lendlein, Dietlind Zohlnhoefer, Constantin Rueder
CLINICAL HEMORHEOLOGY AND MICROCIRCULATION
(2020)
Letter
Cardiac & Cardiovascular Systems
Anna Birukov, Stephanie Wiesemann, Michaela Golic, Andras Balogh, Lajos Marko, Natalia Rakova, Nicola Wilck, Edyta Blaszczyk, Carolin Lim, Sara Weiss, Kristin Kraeker, Nadine Haase, Alina Frolova, Jan Stener Jorgensen, Steffen Daub, Dominik N. Mueller, Florian Herse, Jeanette Schulz-Menger, Ralf Dechend
JACC-CARDIOVASCULAR IMAGING
(2020)
Article
Peripheral Vascular Disease
Hella E. C. Muijsers, Dirk Westermann, Anna Birukov, Olivier W. H. van der Heijden, Jose T. Drost, Kristin Kraeker, Nadine Haase, Dominik N. Mueller, Florian Herse, Angela H. E. M. Maas, Ralf Dechend, Tanja Zeller, Nel Roeleveld
JOURNAL OF HYPERTENSION
(2020)
Article
Peripheral Vascular Disease
Anna Birukov, Florian Herse, Julie H. Nielsen, Henriette B. Kyhl, Michaela Golic, Kristin Kraeker, Nadine Haase, Andreas Busjahn, Signe Bruun, Boye L. Jensen, Dominik N. Mueller, Tina Kold Jensen, Henrik T. Christesen, Marianne Skovsager Andersen, Jan Stener Jorgensen, Ralf Dechend, Louise Bjorkholt Andersen
Article
Multidisciplinary Sciences
Kristin Kraeker, Florian Herse, Michaela Golic, Nadine Reichhart, Sergio Crespo-Garcia, Olaf Strauss, Jana Grune, Ulrich Kintscher, Manal Ebrahim, Michael Bader, Natalia Alenina, Arnd Heuser, Friedrich C. Luft, Dominik N. Mueller, Ralf Dechend, Nadine Haase
SCIENTIFIC REPORTS
(2020)
Article
Peripheral Vascular Disease
Till Schuette, Sarah M. Kedziora, Nadine Haase, Florian Herse, Andreas Busjahn, Anna Birukov, Natalia Alenina, Dominik N. Mueller, Michael Bader, Michael Schupp, Ralf Dechend, Kristin Kraeker, Michaela Golic
Summary: A study conducted on a rat model found that maternal diabetes during pregnancy without obesity did not have a negative impact on the metabolic health of male offspring. There were no significant differences in blood glucose control between offspring exposed to maternal hyperglycemia and those from control pregnancies. Intrauterine exposure to hyperglycemia and hyperinsulinemia without obesity did not lead to fetal programming of diabetes and obesity in this particular model.
Article
Biochemistry & Molecular Biology
Sarah M. Kedziora, Kristin Kraker, Lajos Marko, Julia Binder, Meryam Sugulle, Martin Gauster, Dominik N. Muller, Ralf Dechend, Nadine Haase, Florian Herse
Summary: Preeclampsia is associated with renal injuries during pregnancy, but most of these pathologies often recover postpartum.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Daniel Stehle, Min Ze Xu, Tibor Schomber, Michael G. Hahn, Frank Schweda, Susanne Feil, Jan R. Kraehling, Frank Eitner, Andreas Patzak, Peter Sandner, Robert Feil, Agnes Benardeau
Summary: The study suggests that sGC activators can increase cGMP production in the kidneys under oxidative stress conditions, dilate glomerular arterioles, and improve renal blood flow, making them a promising class of drugs for treating chronic kidney disease.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Till Schuette, Sarah M. Kedziora, Nadine Haase, Florian Herse, Natalia Alenina, Dominik N. Mueller, Michael Bader, Michael Schupp, Ralf Dechend, Michaela Golic, Kristin Kraeker
Summary: Research revealed that diabetic pregnancy affects the cardiac health of rat offspring, particularly under high-fat diet conditions. Offspring of diabetic pregnancies showed cardiac dysfunction and changes in cardiomyocytes after consuming a high-fat diet, highlighting the importance of diet in the development of heart dysfunction in offspring of diabetic pregnancies.
Article
Surgery
Nadia Brunacci, Sebastian Schurmann-Kaufeld, Tobias Haase, Ole Gemeinhardt, Beatrix Schnorr, Melanie Loechel, Isa Rizk, Teo Jimenez, Stephanie Bettink, Bruno Scheller
Summary: The TSS system with radial spikes allows for deeper drug penetration into the arterial wall, effectively inhibiting neointimal proliferation, which was well tolerated.
JOURNAL OF ENDOVASCULAR THERAPY
(2021)
Article
Pharmacology & Pharmacy
Agnes Benardeau, Antje Kahnert, Tibor Schomber, Jutta Meyer, Mira Pavkovic, Axel Kretschmer, Bettina Lawrenz, Elke Hartmann, Ilka Mathar, Joerg Hueser, Jan R. Kraehling, Frank Eitner, Michael G. Hahn, Johannes-Peter Stasch, Peter Sandner
Summary: The study demonstrates that the sGC activator runcaciguat effectively reduces proteinuria, alleviates kidney damage, and improves markers of heart injury in rat CKD models. The treatment approach also shows cardio-renal protection without reducing blood pressure, suggesting its efficiency for CKD and associated cardiovascular diseases.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sarah M. Kedziora, Benedikt Obermayer, Meryam Sugulle, Florian Herse, Kristin Kraeker, Nadine Haase, Immaculate M. Langmia, Dominik N. Muller, Anne Cathrine Staff, Dieter Beule, Ralf Dechend
Summary: The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction caused by diabetes affects placental metabolism, inflammation, and weight, but the main driver of gene expression differences in the placenta is fetal sex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Pilar Palmrich, Nadine Haase, Meryam Sugulle, Erkan Kalafat, Asma Khalil, Julia Binder
Summary: Hypertensive disorders of pregnancy (HDP) are associated with high morbidity and mortality rates in maternal and perinatal health. Despite new insights into the pathophysiology of HDP, the treatment options remain unchanged and there is a lack of evidence for the use of antihypertensive agents to improve outcomes for mothers and newborns.
Meeting Abstract
Medicine, Research & Experimental
Kai Fenzl, Guenter Kramer, Josef J. Auburger, Ilka Mathar, Peter Sandner, Jan R. Kraehling
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Medicine, Research & Experimental
Paul Kiessling, Philipp Ellinger, Florian Sohler, Lars Linden, Peter Sandner, Jan Kraehling
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)