Reactive oxygen species (ROS) are important regulatory molecules implicated in the signaling cascade triggered by tumor necrosis factor (TNF)alpha, although the events through which TNFalpha induces ROS generation are not well characterized. Here, we report that TNFalpha-induced ROS production was blocked by pretreatment with internalization inhibitor monodansyl cadaverine (MDC). Similarly, a transient expression of a GTP-binding and hydrolysis-defective dynamin mutant (dynamin(K44A)) that had been shown to be defective in internalization significantly attenuated the TNFalpha-induced intracellular ROS production. Importantly, the inhibition of receptor internalization suppressed TNFalpha signaling to mitogen-activated protein kinases (MAPKs) stimulation. Together, our results suggest that receptor internalization is somehow necessary for the TNFalpha-induced ROS generation and subsequent intracellular downstream signaling in non-phagocytes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2006.10.154 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacological Characterization of the Novel Selective Kappa Opioid Receptor Agonists 10-Iodo-Akuammicine and 10-Bromo-Akuammicine in Mice.
Neuropharmacology
January 2025
Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. Electronic address:
Akuammicine (AKC), an indole alkaloid, is a kappa opioid receptor (KOR) full agonist with a moderate affinity. 10-Iodo-akuammicine (I-AKC) and 10-Bromo-akuammicine (Br-AKC) showed higher affinities for the KOR with K values of 2.4 and 5.
View Article and Find Full Text PDFA forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.
Dev Cell
January 2025
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.
View Article and Find Full Text PDFBotulinum Toxin: A Comprehensive Review of Its Molecular Architecture and Mechanistic Action.
Int J Mol Sci
January 2025
Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USA.
Botulinum toxin (BoNT), the most potent substance known to humans, likely evolved not to kill but to serve other biological purposes. While its use in cosmetic applications is well known, its medical utility has become increasingly significant due to the intricacies of its structure and function. The toxin's structural complexity enables it to target specific cellular processes with remarkable precision, making it an invaluable tool in both basic and applied biomedical research.
View Article and Find Full Text PDFEstablishment of a Yeast Two-Hybrid-Based High-Throughput Screening Model for Selection of SARS-CoV-2 Spike-ACE2 Interaction Inhibitors.
Int J Mol Sci
January 2025
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
The recent coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted considerable impact on global health. To prepare for rapidly mutating viruses and for the forthcoming pandemic, effective therapies targeting the critical stages of the viral life cycle need to be developed. Viruses are dependent on the interaction between the receptor-binding domain (RBD) of the viral Spike (S) protein (S-RBD) and the angiotensin-converting enzyme 2 (ACE2) receptor to efficiently establish infection and the following replicate.
View Article and Find Full Text PDFDevelopment of a Recombinant Fusion Vaccine Candidate Against Lethal Neurotoxin Types A and B.
Vaccines (Basel)
January 2025
Division of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of Korea.
Background: Botulinum neurotoxins (BoNTs), produced by , are potent protein toxins that can cause botulism, which leads to death or neuroparalysis in humans by targeting the nervous system. BoNTs comprise three functional domains: a light-chain enzymatic domain (LC), a heavy-chain translocation domain (HC), and a heavy-chain receptor-binding domain (HC). The HC domain is critical for binding to neuronal cell membrane receptors and facilitating BoNT internalization via endocytosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!