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)
Article
Pharmacology & Pharmacy
Hasan Slika, Hadi Mansour, Suzanne A. Nasser, Abdullah Shaito, Firas Kobeissy, Alexander N. Orekhov, Gianfranco Pintus, Ali H. Eid
Summary: In 1957, cyclic adenosine monophosphate (cAMP) was identified as the first secondary messenger, and the cAMP-protein kinase A (PKA) pathway was discovered as the first signaling cascade. Recently, a new cAMP effector called exchange protein directly activated by cAMP (Epac) has emerged as a critical mediator of cAMP's actions, playing a role in various diseases and offering potential as a therapeutic target. This paper provides a comprehensive analysis of Epac's structure, distribution, compartmentalization, and signaling mechanisms, discussing the development of specific Epac modulators for future pharmacotherapeutics.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Xuefeng Zhang, Alejandro Pizzoni, Kyoungja Hong, Nyla Naim, Chao Qi, Volodymyr Korkhov, Daniel L. Altschuler
Summary: CAP1 is a highly conserved protein involved in regulating cAMP dynamics in mammalian cells by binding and activating adenylyl cyclase, modulating cAMP levels in a Rap1-dependent manner, and affecting cAMP-dependent proliferation. The interaction between CAP1, cyclase, and Rap1 forms a regulatory unit that may be involved in establishing cAMP microdomains and localized signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Xuemei Sun, Yingnan Wang, Yuchen Zhao, Xinyi Xu, Wenjie Lu, Yuying Li, Fei Bian, Lan Xiang, Lanlan Zhou
Summary: Blood brain barrier (BBB) destruction is crucial in ischemic stroke, leading to BBB leakage and brain edema. The Epac/Rap1 signaling pathway plays a significant role in regulating endothelial cell barrier function. This study investigates the regulatory role of the Epac/Rap1 signaling pathway in BBB disruption after cerebral ischemia/reperfusion (CI/R) injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Aishwarya Krishnan, Aishwarya I. Bhasker, Mithalesh K. Singh, Carlos. I. Rodriguez, Edgardo Castro Perez, Sarah Altameemi, Marcos Lares, Hamidullah Khan, Mary Ndiaye, Nihal Ahmad, Stefan M. Schieke, Vijayasaradhi Setaluri
Summary: EPAC signaling pathway plays a crucial role in the growth and survival of primary melanoma cells. Its inhibition selectively affects cell-cycle proteins and influences the progression of primary melanoma cells. EPAC also regulates glycolysis, oxidative phosphorylation, and production of mitochondrial reactive oxygen species. Loss of dependency on EPAC signaling correlates with melanoma progression, making EPAC a potential prognostic marker and therapeutic target.
MOLECULAR CANCER RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Yunfeng Pan, Jia Liu, Jiahui Ren, Yun Luo, Xiaobo Sun
Summary: This study reviews the regulatory effects of Epac on various vascular diseases, including cardiovascular disease, cerebrovascular disease, and cancer. It suggests that Epac could serve as a promising therapeutic target for the treatment of vascular diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
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
Chemistry, Multidisciplinary
Wen-xia Yang, Yu Liu, Shu-min Zhang, Hua-fen Wang, Yi-fei Liu, Jia-lu Liu, Xiao-hui Li, Meng-ru Zeng, Yu-zhang Han, Fu-you Liu, Lin Sun, Li Xiao
Summary: Epac activation via 8-O-cAMP can ameliorate tubulointerstitial inflammation in DN through the C/EBP-beta/SOCS3/STAT3 pathway, reducing fibrosis in the kidney.
ACTA PHARMACOLOGICA SINICA
(2022)
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)
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
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
Immunology
Xinwei Cao, Yajun Li, Jianrong Shi, Huifang Tang
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosis disease caused by genetic susceptibility and other risk factors. EPAC, as a newly emerging cAMP downstream molecule, plays a vital role in inhibiting fibrosis and may be a novel target for drug development and treatment of IPF.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Liliana Felicia Iannucci, Anna Maria D'Erchia, Ernesto Picardi, Daniela Bettio, Filippo Conca, Nicoletta Concetta Surdo, Giulietta Di Benedetto, Deborah Musso, Cristina Arrigoni, Marco Lolicato, Mauro Vismara, Francesca Grisan, Leonardo Salviati, Luciano Milanesi, Graziano Pesole, Konstantinos Lefkimmiatis
Summary: The study reveals an unexpected mechanism by which EPAC1 enters the nucleus and regulates the transcription of a histone cluster by forming biomolecular condensates in its proximity in response to cAMP.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Xufeng Duan, Yingbo Yang, Aping Yang, Yan Zhao, Fengjuan Fan, Leilei Niu, Nan Hao
Summary: This study demonstrates that terbutaline can alleviate LPS-induced HPMVEC injury through cAMP/Epac signaling, suggesting its potential in the treatment of ALI.
DRUG DEVELOPMENT RESEARCH
(2022)
Editorial Material
Biochemistry & Molecular Biology
Frederic Lagarrigue, Alexandre R. Gingras
Summary: The study identified an intermolecular interaction between two RIAM PH domains that is regulated by Src phosphorylation to unmask the phosphoinositide-binding site, providing insight into the regulation of RIAM plasma membrane translocation for integrin activation.
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.