Background: Although the protooncogenes small GTPases Ras are redox-sensitive proteins, how they are regulated by redox signaling in the central nervous system (CNS) is still poorly understood. Alteration in redox-sensitive targets by redox signaling may have myriad effects on Ras stability, activity and localization. Redox-mediated changes in astrocytic RAS may contribute to the control of redox homeostasis in the CNS that is connected to the pathogenesis of many diseases.
Results And Methods: Here, we investigated the transient physiological induction, at both transcriptional and translational levels, of small GTPases Ras in response to redox stimulation. Cultured astrocytes were treated with hydrogen peroxide as in bolus addition and relative mRNA levels of murine and genes were detected by qRT-PCR. We found that transcription of hras mRNA in reactive astrocytes is redox-sensitive and mimics the prototypical redox-sensitive gene iNOS. Protein abundance in combination with protein turnover measurements by cycloheximide-chase experiments revealed distinct translation efficiency, GTP-bound enrichment, and protein turnover rates between the two isoforms H-Ras and K-Ras.
Conclusion: Reports from recent years support a significant role of H-Ras in driving redox processes. Beyond its canonical functions, Ras may impact on the core astrocytic cellular machinery that operates during redox stimulation.
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http://dx.doi.org/10.1080/13510002.2022.2094109 | DOI Listing |
BMC Res Notes
January 2025
Department of Microbiology and Virology, School of Medicine, Alborz University of Medical Sciences, Alborz, Iran.
Adult T-cell leukemia/lymphoma (ATLL) is a type of blood cancer related to human T-cell lymphotropic virus type 1 (HTLV-1). The principal aim of this study was to investigate cellular processes related to innate immune response, intracellular protein transport, and translational initiation regulation in individuals afflicted with ATLL and Acute lymphoblastic leukemia (ALL). Whole blood samples and peripheral blood mononuclear cells were collected from 10 viral ATLL patients and 10 ALL subjects.
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January 2025
Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Aims: Dedicator of Cytokinesis 2 (DOCK2), a member of the DOCK family of Guanine nucleotide exchange factors that specifically act on the Rho GTPases including Rac and Cdc42, plays pivotal roles in the regulation of leukocyte homeostasis. However, its functions in platelets remain unknown.
Methods And Results: Using mice with genetic deficiency of DOCK2 (Dock2-/-), we showed that Dock2-/-mice exhibited a macrothrombocytopenic phenotype characterized as decreased platelet count and enlarged platelet size by transmission electron microscopy.
Discov Nano
January 2025
Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany.
Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity.
View Article and Find Full Text PDFJ Gastrointest Cancer
January 2025
Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Pancreatic ductal adenocarcinoma is a devastating disease which is associated with an increase in cancer-related death in the USA. The minority of patients are cured by surgery alone and typically require adjuvant chemotherapy in order to improve clinical outcomes. Circulating tumor DNA (ctDNA) is an emerging technology whereby microscopic levels of minimal residual disease (MRD) can be detected in the bloodstream.
View Article and Find Full Text PDFSwiss Med Wkly
January 2025
Cancer Center und Research Center, Cantonal Hospital Graubünden, Chur, Switzerland.
Background And Objective: Because of the lack of effective targeted treatment options, docetaxel has long been the standard second-line therapy for patients with advanced non-small cell lung cancer, including the Kirsten rat sarcoma virus (KRAS) G12C mutation. The CodeBreak 200 trial demonstrated that sotorasib, a new drug targeting the G12C-mutated KRAS protein, modestly improved progression-free survival compared with docetaxel in patients whose cancer had progressed after receiving platinum chemotherapy and programmed cell death protein 1 (PD-1) / programmed death ligand 1 (PD-L1) inhibitors as first-line treatment. Consequently, sotorasib received temporary approval in Switzerland.
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