We have been interested in elucidating the role of intracellular phosphatase activity in the regulation of immune cell activation. To this end, we treated RAW 264.7 murine macrophages with the phosphatase inhibitor, calyculin-A. Treatment with calyculin-A led to activation of IkappaB kinase, degradation of IkappaBalpha, and induced nuclear translocation and DNA binding of NF-kappaB. Each of these effects occurred in both a time- and dose-dependent manner. In addition, each of these effects was negatively modulated by prior induction of the heat-shock response. Despite clear activation of the IkappaB kinase/IkappaBalpha/NF-kappaB pathway, however, phosphatase inhibition did not lead to increased expression of NF-kappaB-dependent genes. Thus, intracellular phosphatase activity is a central regulator of the NF-kappaB signal transduction pathway and is negatively modulated by heat shock. Inhibition of intracellular phosphatase activity with calyculin-A is not sufficient to induce NF-kappaB-dependent gene expression, demonstrating the complexity of NF-kappaB regulation in immune cells.
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http://dx.doi.org/10.1016/s0006-291x(02)02373-2 | DOI Listing |
Ecotoxicol Environ Saf
January 2025
National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China. Electronic address:
Obesity is a contributing factor that increases the likelihood of developing chronic kidney disease. In recent years, studies have found that light pollution worldwide promoted obesity, which was known to be a consequence of circadian rhythm disruption. Nevertheless, the impact of light pollution on kidney disease associated with obesity remains mostly unknown, and potential processes have been minimally investigated.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman university of Medical Sciences, Kerman, Iran.
Lung Ischemia-reperfusion injury (LIRI) is a risk during lung transplantation that can cause acute lung injury and organ failure. In LIRI, the NF-E2-related factor 2(Nrf2)/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway are two major pathways involved in regulating oxidative stress and inflammation, respectively. Myrtenol, a natural compound with anti-inflammatory and antioxidant properties, has potential protective effects against IRI.
View Article and Find Full Text PDFVet Med Sci
January 2025
Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
The present study aimed to unveil the gastroprotective potential of Vaccinium macrocarpon (VM) extract and its mechanism of action against indomethacin (INDO)-induced gastric ulcers in rats. To achieve this goal, rats were pretreated with either omeprazole (20 mg/kg) or VM (100 mg/kg) orally for 14 consecutive days. Gastric tissue samples were collected and various parameters were evaluated to understand the mechanism of VM's action, including the levels of superoxide dismutase, malondialdehyde, glutathione, CAT and transforming growth factor beta (TGF-β), as well as the mRNA expression levels of tumour necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B (NF-κB) and inhibitor kappa B (IκB).
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, 650500, China. Electronic address:
Acne is a prevalent and chronic inflammatory skin disease, and its treatment remains a huge clinical challenge. In the present study, we evaluated the therapeutic potential of combining the peptides RL-QN15 and OH-CATH30 for the treatment of acne in mice. Results indicated that the topical application of RL-QN15 and OH-CATH30 significantly inhibited the proliferation of Propionibacterium acnes (P.
View Article and Find Full Text PDFBioorg Chem
December 2024
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Ningbo Institute of Marine Medicine, Peking University, Beijing 100191, PR China. Electronic address:
Prenylated indole diketopiperazines represent a diverse array of alkaloids with complex chemical scaffolds and with a wide range of biological activities. Aiming to discover bioactive metabolites with structural novelty, genomic annotation in association with the MS/MS-based molecular networking demonstrated a deep-sea derived fungus Aspergillus puulaauensis F77 containing a profile of diketopiperazines. Targeted separation of the cultured fungus led to the isolation of 19 undescribed austamide-type diketopiperazines namely versicoines A-S.
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