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Cell Biology
Xiaokan Zhang, Bryan Z. Wang, Michael Kim, Trevor R. Nash, Bohao Liu, Jenny Rao, Roberta Lock, Manuel Tamargo, Rajesh Kumar Soni, John Belov, Eric Li, Gordana Vunjak-Novakovic, Barry Fine
Summary: Protein kinase A (PKA) is critical for cardiac function, but its activity is tightly regulated. In this study, we identified STK25 as a kinase of PRKAR1A, a regulatory subunit of PKA. Phosphorylation of PRKAR1A inhibits PKA activity and increases binding to the catalytic subunit. Knockout of Stk25 in mice leads to decreased Prkar1a phosphorylation, increased Pka activity, and enhanced response to beta-adrenergic stimulation. These findings suggest that STK25 acts as a negative regulator of PKA signaling through phosphorylation of PRKAR1A.
Article
Multidisciplinary Sciences
Kazuki Yoshida, Shota Tanihara, Yuki Miyashita, Kosuke Obayashi, Masa-Aki Ito, Kimiko Yamamoto, Toshiyashu Imai, Isao Matsuoka
Summary: Extracellular ATP enhances MC activation induced by MrgprB2 through P2X4 receptor-mediated signaling pathway, which may be a potential target for alleviating pseudoallergic reactions.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Karthik Ramachandran, Soumya Maity, Alagar R. Muthukumar, Soundarya Kandala, Dhanendra Tomar, Tarek Mohamed Abd El-Aziz, Cristel Allen, Yuyang Sun, Manigandan Venkatesan, Travis R. Madaris, Kevin Chiem, Rachel Truitt, Neelanjan Vishnu, Gregory Aune, Allen Anderson, Luis Martinez, Wenli Yang, James D. Stockand, Brij B. Singh, Subramanya Srikantan, W. Brian Reeves, Muniswamy Madesh
Summary: SARS-CoV-2 infection causes significant changes in cellular components such as mitochondria, ion channels, and protein quality control. The viral proteins selectively target cellular organelles, including the endoplasmic reticulum and mitochondria. Cyclosporin A has been found to alleviate cell death and cardiomyocyte damage.
Article
Biochemistry & Molecular Biology
Aina Porta, Laura Rodriguez, Xue Bai, Gerard Batalle, Gerad Roch, Enric Pouso-Vazquez, Gianfranco Balboni, Olga Pol
Summary: This study demonstrates that slow-releasing H2S donors can inhibit allodynia and hyperalgesia, potentiate the analgesic effects and expression of DOR, activate the antioxidant system, and reduce nociceptive and apoptotic pathways in inflammatory pain models. The data also suggest the involvement of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. Systemic administration of DADS and P-ITC, along with local application of DOR agonists in combination with H2S donors, offer new strategies for the treatment of inflammatory pain.
Article
Biochemistry & Molecular Biology
Jir-You Wang, Chao-Ming Chen, Cheng-Fong Chen, Po-Kuei Wu, Wei-Ming Chen
Summary: Osteosarcoma is a highly malignant musculoskeletal tumor commonly seen in various age groups, with a survival rate of 70-80%. ER alpha plays a significant role in osteosarcoma pathogenesis and chemosensitivity, with potential as a target for current treatments and a prognostic factor for chemotherapy response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sergey A. Menzikov, Danila M. Zaichenko, Aleksey A. Moskovtsev, Sergey G. Morozov, Aslan A. Kubatiev
Summary: The intracellular chloride concentration plays a crucial role in GABA(A)R-mediated neurotransmission, involving both synaptic and extrasynaptic inhibition as well as excitation. The direction of Cl(-) and HCO3- fluxes is determined by underlying electrochemical gradient controlled by transporters and channels. The discovery of a GABA(A)R type requiring ATP consumption for chloride movement sheds new light on inhibitory signaling mechanisms.
Article
Immunology
Zhiwei Li, Frieder Hadlich, Klaus Wimmers, Eduard Murani
Summary: This study investigates the consequences of glucocorticoid receptor (GR) hypersensitivity during infection and provides insights into the impact of GR hypersensitivity on the fate and function of immune cells. The study found that a specific genetic variant of GR, Ala610Val, aggravates the response to endotoxemia in pigs and amplifies inflammatory responses. However, this variant also orchestrates genes involved in anti-inflammatory responses during infection, suggesting potential therapeutic applications in endotoxemia treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Xue-Lian Qi, Ruifeng Liu, Balbir Singh, David Bestue, Albert Compte, Almira Vazdarjanova, David T. Blake, Christos Constantinidis
Summary: Acetylcholine in the neocortex plays a critical role in enhancing cognitive functioning. Stimulation of the nucleus basalis affects working memory and alters neural coding. Despite a decrease in neuronal selectivity after stimulation, performance improves in many task conditions, likely indicating increased delay period stability.
Article
Oncology
Emiliano Roselli, Justin C. Boucher, Gongbo Li, Hiroshi Kotani, Kristen Spitler, Kayla Reid, Estelle Cervantes, Yannick Bulliard, Nhan Tu, Sae Bom Lee, Bin Yu, Frederick L. Locke, Marco L. Davila
Summary: The study demonstrates that combining 4-1BB with an optimized form of CD28 for co-stimulation is an effective way to enhance CAR T cell function. Both mono-specific and bi-specific versions of this design show improved expansion, persistence, and resistance to exhaustion in vitro and in vivo.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Domenico Azarnia Tehran, Gaga Kochlamazashvili, Niccolo P. Pampaloni, Silvia Sposini, Jasmeet Kaur Shergill, Martin Lehmann, Natalya Pashkova, Claudia Schmidt, Delia Loewe, Hanna Napieczynska, Arnd Heuser, Andrew J. R. Plested, David Perrais, Robert C. Piper, Volker Haucke, Tanja Maritzen
Summary: This study reveals that the Alzheimer's disease risk factor CALM controls the surface levels of CP-AMPARs through endocytosis, and this regulation reciprocally modulates LTP and LTD in vivo to influence learning.
Review
Neurosciences
Shan P. Yu, Michael Q. Jiang, Seong S. Shim, Soheila Pourkhodadad, Ling Wei
Summary: Stroke and late-onset Alzheimer's disease (AD) are risk factors for each other. The similarities and differences between the two in terms of pathogenesis and pathophysiology have rarely been reviewed. Recent research has found that the activation of NMDA receptors and the resulting calcium influx play an important role in both stroke and AD. Blocking extrasynaptic NMDA receptors with drugs like memantine could serve as a potential treatment option for both diseases.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Veerle Lemmens, Bart Thevelein, Yana Vella, Svenja Kankowski, Julia Leonhard, Hideaki Mizuno, Susana Rocha, Bert Brone, Jochen C. Meier, Jelle Hendrix
Summary: In this study, the researchers used fluorescence microscopy and electrophysiology analysis to demonstrate that splice variants of GlyR-alpha 3 can heteropentamerize and exhibit properties between those of K and L variants. This study is important for understanding and addressing diseases related to GlyR-alpha 3.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Nicole Urban, Marion Leonhardt, Michael Schaefer
Summary: This study identified and characterized novel agonists of GPER1/GPR30 receptor, showing that GPR30 couples to the canonical Gq-phospholipase C pathway and undergoes rapid internalization upon continuous exposure to the agonists. These findings provide insights into the physiological responses controlled by GPR30.
MOLECULAR PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jun-Dal Kim, Chulwon Kwon, Kanako Nakamura, Naoto Muromachi, Haruka Mori, Shin-ichi Muroi, Yasunari Yamada, Hodaka Saito, Yoshimi Nakagawa, Akiyoshi Fukamizu
Summary: Cardiac hypertrophy is a significant risk factor for hypertensive disorders during pregnancy, and the factors involved in its progression have been investigated in a mouse model. The study found that decreased levels of Adra1a, an adrenergic receptor, and upregulation of the renin-angiotensin system were associated with progressive cardiac hypertrophy. Furthermore, Adra1a-deficient mice showed more severe hypertrophy, suggesting the involvement of Adra1a expression in the development of cardiac hypertrophy in hypertensive disorders during pregnancy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Masa-aki Ito, Erika Kojima, Yu Yanagihara, Kazuki Yoshida, Isao Matsuoka
Summary: This study compared the physiological effects mediated by different Gq-binding uridine nucleotide receptors and found that IL-8 production induced by the P2Y(6) receptor requires Gq-mediated calcium signaling and G(12)-mediated Rac activation.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)