Article
Biochemistry & Molecular Biology
Yan-Yan Zhao, Li-Jun Zhang, Xiang-Yan Liang, Xiao-Chun Zhang, Jin-Rui Chang, Man Shi, Huan Liu, Ying Zhou, Zhuo Sun, Yu-Feng Zhao
Summary: Pyruvate activates PDEs to reduce cAMP levels and inhibits the cAMP-Epac-CREB signaling pathway, resulting in upregulation of FGF21 expression in hepatocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Agnieszka Kilanowska, Agnieszka Ziolkowska, Piotr Stasiak, Magdalena Gibas-Dorna
Summary: The cAMP-dependent pathway plays a significant role in ovarian cells, regulating gene expression and cellular functions. It is associated with ovarian cancer development, metastasis, and survival. Targeting specific stages of this pathway may offer promising therapeutic opportunities for ovarian cancer patients.
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.
Review
Endocrinology & Metabolism
Graeme B. Bolger
Summary: cAMP-signaling cancers are driven by somatic mutations in the cAMP signaling pathway genes, resulting in a wide range of cell origins, clinical manifestations, and potential therapeutic options. The tumor phenotype is influenced by the specific gene mutations, allele effects, mutational context, tissue-specific expression, and biochemical regulation of the pathway components. Understanding these oncogenic mechanisms can lead to the discovery of novel drug targets.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Plant Sciences
Ranran Wang, Lulu Wei, Junaid Wazir, Li Li, Shiyu Song, Kai Lin, Wenyuan Pu, Chen Zhao, Zhonglan Su, Quan Zhao, Hongwei Wang
Summary: Curcumin improves adipose atrophy in cancer cachexia by inhibiting the cAMP/PKA/CREB signaling pathway. The study shows that curcumin protects mice with C26 tumors and cachexia from weight loss and adipose atrophy, reducing levels of free fatty acids and increasing triglyceride levels. Curcumin also ameliorates CL316243-induced adipose atrophy and inhibits hormone-mediated PKA and CREB activation.
Article
Virology
Shilin Gong, Xianhui Hao, Yanhong Bi, Chenchen Yang, Wenjing Wang, Houfack K. Mickael, Yike Zhang, Shuangfeng Chen, Zhongyao Qian, Fen Huang, Daqiao Wei, Wenhai Yu
Summary: HEV infection significantly inhibits the cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways, but not the Ras-Raf-MEK-ERK pathway. Elevated estrogen levels and highly activated ER alpha during pregnancy exacerbate HEV replication. This exacerbation further inhibits ER alpha expression and suppresses cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Nutrition & Dietetics
Hai-Lan Li, Mei-Jin Li, Guang-Quan Xiong, Jun Cai, Tao Liao, Xiao-Yan Zu
Summary: This study investigated the mechanism of silver carp scale collagen peptides (SCPs1) on melanogenesis in mouse melanoma cells (B16). SCPs1 inhibited melanin synthesis by downregulating the cAMP-CREB signaling pathway, which led to decreased expression of melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TRP-1), and TRP-2.
Article
Pharmacology & Pharmacy
Rongyin Gao, Ximei Zhang, Kun Zou, Duo Meng, Jinpeng Lv
Summary: Recent research indicates that clock proteins, specifically the protein CRY, play a role in regulating cutaneous pigmentation. The synthetic molecule modulator KL001 was found to inhibit melanin synthesis and reduce melanocyte dendrite elongation and melanosome transport. Activation of CRY1 led to the downregulation of MITF through the cAMP/PKA pathway, resulting in the inhibition of melanogenesis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Qian Zhou, Ying Zhang, Lu Lu, Wei Shi, Hu Zhang, Weizhuo Qin, Yucheng Wang, Yuepu Pu, Lihong Yin
Summary: It has been widely reported that long-term exposure to copper increases the prevalence and mortality of Parkinson's disease. Our previous study showed that CuSO4 exposure induced a significant increase in the expression of cleaved Caspase1 proteins and the loss of dopaminergic neurons in the SNpc of mice. In this study, the effects of copper(II) on cAMP/PKA/CREB pathway and pyroptosis-related proteins in MN9D cells were investigated to provide possible molecular evidence for studying the mechanism of copper(II)-induced degeneration of dopaminergic neurons.
Article
Biotechnology & Applied Microbiology
Itishree Kaushik, Sanjay K. Srivastava
Summary: In this study, moxidectin, a GABAA receptor agonist, was found to inhibit the proliferation of Sonic hedgehog-activated subgroup of medulloblastoma (SHH-MB) cells by inducing apoptosis. Moxidectin also suppressed the expression of related signaling pathways and cancer stem cell molecules. In mouse models, oral administration of moxidectin significantly suppressed the growth of SHH-MB tumors. These findings suggest that moxidectin may be a potential therapeutic option for treating SHH-MB patients.
Article
Biochemistry & Molecular Biology
Jan N. Hansen, Fabian Kaiser, Philipp Leyendecker, Birthe Stueven, Jens-Henning Krause, Fatemeh Derakhshandeh, Jaazba Irfan, Tommy J. Sroka, Kenley M. Preval, Paurav B. Desai, Michael Kraut, Heidi Theis, Anna-Dorothee Drews, Elena De-Domenico, Kristian Haendler, Gregory J. Pazour, David J. P. Henderson, David U. Mick, Dagmar Wachten
Summary: This article investigates how the primary cilium controls cellular functions and tissue integrity through the ciliary cAMP signalosome, and reveals novel molecular components that may be involved in the development of polycystic kidney disease.
Article
Peripheral Vascular Disease
Lara Matilla, Eva Jover, Mattie Garaikoetxea, Ernesto Martin-Nunez, Vanessa Arrieta, Amaia Garcia-Pena, Adela Navarro, Amaya Fernandez-Celis, Alicia Gainza, Virginia Alvarez, Diego Alvarez de la Rosa, Rafael Sadaba, Frederic Jaisser, Natalia Lopez-Andres
Summary: There are sex differences in the pathophysiology of aortic valve (AV) calcification in patients with aortic stenosis. Aldosterone (Aldo) promotes proteoglycan synthesis in valve interstitial cells (VICs) via the mineralocorticoid receptor (MR). The MR/Aldo pathway plays a role in fibrosis in women and in early AV calcification in men.
Article
Biochemistry & Molecular Biology
Hye Yeon Lim, Eunji Kim, Sang Hee Park, Kyung Hwan Hwang, Donghyun Kim, You-Jung Jung, Spandana Rajendra Kopalli, Yong Deog Hong, Gi-Ho Sung, Jae Youl Cho
Summary: Theasinensin A (TSA) has been shown to inhibit melanin formation and secretion, as well as down-regulate the expression of genes related to melanin formation. TSA can also suppress the activities of proteins in the melanocortin 1 receptor (MC1R) signaling pathway associated with melanin synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Jiazhen Wu, Yuxuan Gan, Huijuan Luo, Nan Xu, Liping Chen, Mengyao Li, Fengkun Guan, Ziren Su, Zhixiu Lin, Jianhui Xie, Yuhong Liu
Summary: The study found that beta-patchoulene can significantly improve symptoms of intestinal mucositis, mainly by improving water transport and mucus barrier to alleviate diarrhea.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Mingqiang Wang, Yanzhen Li, Jianhui Su, Jingyan Bai, Zhongxiang Zhao, Zhanghua Sun
Summary: This study found that 4-GDB can alleviate colonic injury, reduce inflammation, and improve colonic barrier function by regulating cAMP/PKA/CREB and NF-kappa B pathways. This suggests that 4-GDB may be a potential agent for treating ulcerative colitis.
PHYTOTHERAPY RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Barbara Schreier, Alexander Zipprich, Henriette Uhlenhaut, Michael Gekle
Summary: This narrative review summarizes the role of mineralocorticoid receptor (MR) in liver diseases and suggests that inhibiting MR in vivo may be beneficial for liver function. However, the underlying molecular mechanisms of MR in liver diseases are still not completely understood.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Barbara Schreier, Virginie Dubourg, Stefanie Huebschmann, Sindy Rabe, Sigrid Mildenberger, Michael Gekle
Summary: The study reveals that EGFR and AT1R synergistically regulate gene expression, leading to qualitative, quantitative, and temporal changes, potentially impacting cell stress and vascular biology. Synergistic activation of SRF via distinct pathways and transcription factors AP1 and EGR plays a key role in this process.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Stefanie Ruhs, Bruno Griesler, Ralf Huebschmann, Katharina Stroedecke, Nicole Straetz, Christian Ihling, Andrea Sinz, Antonia Masch, Mike Schutkowski, Michael Gekle, Claudia Grossmann
Summary: This study found that casein kinase 1 (CK1) acts as a co-activator of mineralocorticoid receptor (MR) GRE activity through direct and indirect phosphorylation. It accelerates the cytosolic-nuclear trafficking of MR, facilitates its nuclear accumulation and DNA binding, and increases the expression of MR-target genes that are relevant to pathological conditions.
Article
Biochemistry & Molecular Biology
Heike Braun, Michael Hauke, Robert Eckenstaler, Markus Petermann, Anne Ripperger, Niklas Kuehn, Edzard Schwedhelm, Beatrice Ludwig-Kraus, Frank Bernhard Kraus, Virginie Dubourg, Alma Zernecke, Barbara Schreier, Michael Gekle, Ralf A. Benndorf
Summary: The study found that vascular smooth muscle cell (VSMC)-specific TP deletion attenuated atherogenesis in mice, without impacting blood pressure or lipid profiles. Additionally, 8-iso-PGF2 alpha appears to reduce atherogenesis in Ldlr-deficient mice, especially in those lacking EC-specific TP. This suggests that the TP expressed in VSMC is involved in atherosclerotic lesion formation and 8-iso-PGF2 alpha has an inhibitory effect on atherogenesis in this experimental model.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Marie-Christin Schulz, Linda Voss, Gerald Schwerdt, Michael Gekle
Summary: The pathogenesis of chronic kidney disease involves extracellular acidosis, inflammation, fibrosis, and epithelial-to-mesenchymal transition (EMT). This study examined the effects of acidosis on tubule epithelial cells and fibroblasts and explored the role of cell crosstalk in these effects. Acidosis led to increased inflammation, EMT, and fibrosis; however, in co-culture, these effects were reversed or inhibited. The intercellular crosstalk between epithelial cells and fibroblasts was found to have a protective function in acidosis-induced damage.
Article
Cell Biology
Virginie Dubourg, Barbara Schreier, Gerald Schwerdt, Sindy Rabe, Ralf A. Benndorf, Michael Gekle
Summary: This study investigates the interaction between the Epidermal Growth Factor Receptor (EGFR) and the Angiotensin-II (AT1R) or Thromboxane-A2 (TP) receptors in murine primary aortic vascular smooth muscle cells. The results show that the simultaneous activations of EGFR-AT1R or EGFR-TP lead to different patterns of regulated genes compared to individual receptor activations. Furthermore, the combined EGFR-TP activation causes a variation in amplitude regulation for specific genes, including those relevant to vascular injury.
Article
Virology
Christoph Schultheiss, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Michael Gekle, Rafael Mikolajczyk, Mascha Binder
Summary: Post-acute sequelae of COVID-19 (PASC) are long-term consequences of SARS-CoV-2 infection that significantly impact life quality. This study reveals pronounced dysregulation in immune factors and persistence of viral protein in individuals with PASC, highlighting its biological heterogeneity. Further correlation with clinically defined PASC subtypes is needed.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Psychiatry
Janka Massag, Sophie Diexer, Bianca Klee, Daniela Costa, Cornelia Gottschick, Anja Broda, Oliver Purschke, Nils Opel, Mascha Binder, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica Hoell, Irene Moor, Jonas Rosendahl, Michael Gekle, Rafael Mikolajczyk
Summary: The Russian invasion of Ukraine has had a negative impact on the mental health of the German population, with anxiety and distress levels remaining elevated even after 6 months. Low-income individuals, especially those experiencing fears related to their personal financial situation, were most affected. Those who initially reacted strongly with fear were more likely to experience persistent symptoms of depression and anxiety.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Marie-Christin Schulz, Virginie Dubourg, Alexander Nolze, Michael Kopf, Gerald Schwerdt, Michael Gekle
Summary: The crosstalk between renal epithelial cells and interstitial fibroblasts in the kidney plays an important role in kidney pathophysiology. Acidosis enhances the cytoprotective Nrf2 pathway in renal epithelial cells co-cultivated with renal fibroblasts, leading to increased expression of the cytoprotective TKT. This protective response is not observed in monoculture.
Article
Psychiatry
Cornelia Gottschick, Sophie Diexer, Janka Massag, Bianca Klee, Anja Broda, Oliver Purschke, Mascha Binder, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. I. Hoell, Patrick Michl, Michael Gekle, Rafael Mikolajczyk
Summary: During the Russo-Ukrainian war, the German population experienced significant distress and anxiety due to the exposure to media reports of violence. Fear of the impact of war was associated with worse mental health, surpassing the reactions during the strictest COVID-19 restrictions.
Article
Infectious Diseases
Sophie Diexer, Bianca Klee, Cornelia Gottschick, Chao Xu, Anja Broda, Oliver Purschke, Mascha Binder, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Irene Moor, Michael Gekle, Rafael Mikolajczyk
Summary: The Omicron variant of the SARS-CoV-2 virus has become the dominant strain since 2022 and is associated with milder acute infection compared to previous variants. However, little is known about the occurrence of long-term symptoms after Omicron infection and how it is influenced by previous infections and/or vaccinations.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Virginie Dubourg, Marie-Christin Schulz, Philipp Terpe, Stefanie Ruhs, Michael Kopf, Michael Gekle
Summary: Extracellular acidosis has a significant impact on the transcriptional activity of non-tumor cells, leading to quantitative transcriptional alterations in different cell types. The regulator NCOA5 is identified as the only general acidosis-responsive gene. Gene Ontology enrichment analysis and upstream regulator analysis suggest a general acidosis response pattern involving the integrated stress response, TGF-β signaling, NFE2L2, and TP53.
Article
Mycology
Gerald Schwerdt, Michael Kopf, Michael Gekle
Summary: Despite previous research, the exact mechanism of action of ochratoxin A (OTA) still remains unclear. In this study, we observed that cells exposed to OTA exhibited increased glucose consumption and lactate production, indicating a potential involvement of cellular metabolism and mitochondria. Our findings suggest that OTA exposure impairs mitochondrial function, leading to a shift in cellular metabolism towards anaerobic glycolysis, which is supported by increased glucose uptake and glycogen degradation. We propose considering the impact of OTA on metabolism and mitochondria, as well as analyzing OTA-induced changes in the metabolome, as additional factors contributing to OTA toxicity.
MYCOTOXIN RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Barbara Schreier, Christian Stern, Sindy Rabe, Sigrid Mildenberger, Michael Gekle
Summary: In this study, the role of EGFRs in VSMCs and ECs for blood pressure homeostasis and acute vascular reactivity was investigated. The findings suggest that VSMC-EGFR has a significant impact on blood pressure changes induced by volume load, while EC-EGFR has a minor role in blood pressure regulation. Moreover, there is no significant difference in the response to AII and catecholamine stimulation between lean and obese animals, indicating that obesity and high-fat diet do not significantly affect these mechanisms.
Article
Cell Biology
Christoph Schultheiss, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Svenja-Sibylla Henkes, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Michael Gekle, Rafael Mikolajczyk, Mascha Binder
Summary: Post-acute sequelae of COVID-19 (PASC) is a global problem with unknown molecular drivers. A study found that 67.8% of participants, mostly with mild infections, reported PASC, with symptoms including fatigue, dyspnea, and concentration deficit. These symptoms persisted in 60% of participants over an average 8-month follow-up period. PASC was associated with elevated plasma levels of IL-18, IL-6, and TNF.
CELL REPORTS MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Olexander M. Semenenko, Victoria V. Lipson, Alina O. Sadchenko, Olga V. Vashchenko, Natalia A. Kasian, Liliia Sviechnikova, Longin M. Lisetski, Mykola L. Babak, Volodymyr M. Vakula, Oleksandr Borysov, Yuliia Holota, Sergey O. Zozulya, Petro O. Borysko, Olexander Mazepa
Summary: An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids has been developed and their structures and properties have been fully established. The hybrids showed inferior interactions with artificial lipid membranes, possibly due to their increasing lipophilicity.
Article
Biochemistry & Molecular Biology
Mohadese Yaghoobi Anzabi, Piotr Cmoch, Roman Luboradzki, Zbigniew Pakulski
Summary: Friedelin and 3-acetoxyfriedel-3-en-2-one, known as friedelane triterpenoids, have been isolated from cork smoker wash solids and used as starting materials for the synthesis of new friedelane derivatives. Reduction reactions result in the formation of friedelinol and epi-cerin derivatives.
Article
Biochemistry & Molecular Biology
Detlef Thieme, Aniko Krumbholz, Martin Bidlingmaier, Christoph Geffert, Annika Hameder, Andreas Stoever, Matthias Graw, Annekathrin M. Keiler
Summary: Ethanol can affect testosterone metabolism and potentially influence steroid biosynthesis and blood steroid profiles. The study emphasizes the importance of sufficient time interval from food and ethanol intake during blood sampling, particularly for diagnostics in doping control.
Article
Biochemistry & Molecular Biology
Masanobu Murao, Tetsuo Imano, Yoshinobu Sato, Masaaki Nakajima
Article
Biochemistry & Molecular Biology
Jingyuan Wang, Ye Feng, Brian Liu, Wen Xie
Summary: Sulfation and desulfation of steroids are opposing processes that regulate steroid homeostasis and are involved in steroid-related diseases. Cytosolic sulfotransferase and steroid sulfatase modify and regulate steroids to affect hormonal dysregulation, metabolic diseases, and cancer.
Article
Biochemistry & Molecular Biology
Noah K. Babel, Brian J. Feldman
Summary: Our research identified a previously unrecognized ADAMTS1-PTN-Wnt pathway in regulating adipose precursor cell behavior. The non-muscle myosin protein MYH9 was found to be a key target of this pathway for modulating adipogenesis. These findings offer potential for developing novel therapeutics for obesity and related metabolic disorders.
Article
Biochemistry & Molecular Biology
Martiniano Bello
Summary: This study explores the structural and thermodynamic basis of molecular recognition between ERβ and DPN and its derivatives using molecular dynamics simulations and end-point methods. The results show that the MMGBSA approach is able to reproduce experimental trends and identify eight residues that strongly interact with the ligands.
