In response to ambient hypertonicity, TonEBP (tonicity-responsive enhancer binding protein) stimulates certain genes including those encoding cytokines, transporters for organic solutes, and a molecular chaperone. TonEBP is regulated in a bidirectional manner, upregulated by an increase in ambient tonicity while downregulated by a decrease. To investigate the role of intracellular ionic strength in the activity of TonEBP, we subjected Madin-Darby canine kidney cells to a variety of conditions. Electron microprobe analysis was performed to measure intracellular electrolytes. Under conditions in which changes in cell volume were similar, TonEBP activity correlated with the intracellular ionic strength regardless of the external tonicity. On the other hand, inhibition of the Na+/K+-ATPase and high external K+ concentration led to a decreased activity of TonEBP despite a marked increase in the intracellular ionic strength. Because isotonic swelling is known to occur under these conditions, these data suggest that dilution of the cytoplasmic constituents inhibits the activity of TonEBP. We conclude that intracellular ionic strength and water content are major factors that determine the activity of TonEBP.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajpcell.00216.2002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mitochondria as a Therapeutic Target: Focusing on Traumatic Brain Injury.
J Integr Neurosci
January 2025
Department of Hepatology, Federal University of Health Sciences of Porto Alegre (UFCSPA), 90050-170 Porto Alegre, Rio Grande do Sul (RS), Brazil.
Mitochondria are organelles of eukaryotic cells delimited by two membranes and cristae that consume oxygen to produce adenosine triphosphate (ATP), and are involved in the synthesis of vital metabolites, calcium homeostasis, and cell death mechanisms. Strikingly, normal mitochondria function as an integration center between multiple conditions that determine neural cell homeostasis, whereas lesions that lead to mitochondrial dysfunction can desynchronize cellular functions, thus contributing to the pathophysiology of traumatic brain injury (TBI). In addition, TBI leads to impaired coupling of the mitochondrial electron transport system with oxidative phosphorylation that provides most of the energy needed to maintain vital functions, ionic homeostasis, and membrane potentials.
View Article and Find Full Text PDFOsmotic stress influences microtubule drug response via WNK1 kinase signaling.
Drug Resist Updat
January 2025
Cell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid 28029, Spain; Translational Cancer Research Group, Chronic Diseases and Cancer, Area 3, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; UCLM Biomedicine Unit Associated to CSIC, Spain; CSIC Conexión-Cáncer Hub, Spain. Electronic address:
Ion homeostasis is critical for numerous cellular processes, and disturbances in ionic balance underlie diverse pathological conditions, including cancer progression. Targeting ion homeostasis is even considered as a strategy to treat cancer. However, very little is known about how ion homeostasis may influence anticancer drug response.
View Article and Find Full Text PDFPhysiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release.
J Physiol Sci
January 2025
National Institute for Physiological Sciences (NIPS), 5-1 Higashiyama, Myodaiji, 444-8787, Okazaki, Aichi, Japan; Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita, Japan; Department of Physiology, School of Medicine, Aichi Medical University, Nagakute, Japan; Graduate University for Advanced Studies (SOKENDAI), Hayama, Kanagawa, Japan. Electronic address:
The volume-sensitive outwardly rectifying or volume-regulated anion channel, VSOR/VRAC, which was discovered in 1988, is expressed in most vertebrate cell types, and is essentially involved in cell volume regulation after swelling and in the induction of cell death. This series of review articles describes what is already known and what remains to be uncovered about the functional and molecular properties as well as the physiological and pathophysiological roles of VSOR/VRAC. This Part 2 review article describes, from the physiological and pathophysiological standpoints, first the pivotal roles of VSOR/VRAC in the release of autocrine/paracrine organic signal molecules, such as glutamate, ATP, glutathione, cGAMP, and itaconate, as well as second the swelling-independent and -dependent activation mechanisms of VSOR/VRAC.
View Article and Find Full Text PDFEmerging Role of Noncovalent Interactions and Disulfide Bond Formation in the Cellular Uptake of Small Molecules and Proteins.
Chem Asian J
January 2025
Indian Institute of Science, Inorganic and Physical Chemistry, Indian Institute of Science, 560 012, Bangalore, INDIA.
Intracellular delivery of proteins is an important barrier in the development of strategies to deliver functional proteins and protein therapeutics into the cells to realize their full potential in biotechnology, biomedicine, cell-based therapies, and gene editing protein systems. Most of the intracellular protein delivery strategies involve the conjugation of cell penetrating peptides to enable and enhance the permeability of plasma membrane of mammalian cells to allow proteins to enter cytosol. Small molecules conjugations such as (p-methylphenyl) glycine, pyrenebutyrate and cysteines are used for the same purpose.
View Article and Find Full Text PDFSequential pH/GSH-responsive stealth nanoparticles for co-delivery of anti-PD-1 antibody and paclitaxel to enhance chemoimmunotherapy of lung cancer.
Eur J Med Chem
January 2025
Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. Electronic address:
Intravenously administered nanoparticles (NPs) often bind with plasma proteins, forming the protein corona that promotes rapid systemic clearance, a primary challenge in nanomedicine. In this study, we developed a pH- and GSH-sensitive "stealth" nanodelivery system, PTX@NPs-aPD1-IL, for sequential drug release. By using a biocompatible choline-based ionic liquid (IL) as the coating for NPs, the interaction and adsorption of NPs with serum proteins were reduced, achieving targeted delivery to the lung organ and increasing drug accumulation.
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!