Related Experiment Video

Updated: Aug 1, 2026

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

Formation of ion-permeable channels by tumor necrosis factor-alpha

B L Kagan1, R L Baldwin, D Munoz

  • 1Department of Psychiatry, School of Medicine, University of California, Los Angeles 90024.

Science (New York, N.Y.)
|March 13, 1992
PubMed

Insights

Tumor necrosis factor-alpha (TNF) may exert its effects by forming ion channels. Acidification induces conformational changes, enabling TNF to form pH-dependent channels in lipid bilayers and increase cell ion permeability.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Immunology

Background:

  • Tumor necrosis factor-alpha (TNF) is a protein involved in inflammatory and disease states.
  • The precise mechanisms of TNF's cytotoxic and hormonal effects are not fully understood.
  • Structural analysis suggests TNF trimers have a pore-like region, hinting at channel activity.

Purpose of the Study:

  • To investigate the potential ion channel-forming activity of TNF.
  • To explore the structural and functional properties of TNF in lipid environments.
  • To determine if TNF's physiological effects are mediated by ion channel formation.

Main Methods:

  • Conformational change analysis of TNF upon acidification.
  • Lipid vesicle insertion assays.
  • Planar lipid bilayer electrophysiology to assess ion permeability.
  • Measurement of sodium permeability in U937 lymphoma cells.

Main Results:

  • Acidification induced conformational changes in TNF, increasing surface hydrophobicity and membrane insertion.
  • TNF formed pH-dependent and voltage-dependent ion-permeable channels in artificial lipid bilayers.
  • TNF increased sodium ion permeability in human U937 cells.

Conclusions:

  • TNF possesses intrinsic ion channel-forming activity.
  • This activity is influenced by pH and voltage.
  • TNF's physiological effects may be partly mediated by its ion channel function.

More Related Videos

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis09:42

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis

Published on: June 26, 2019

Screening Ion Channels in Cancer Cells06:19

Screening Ion Channels in Cancer Cells

Published on: June 16, 2023

Related Concept Videos

Ion Channels01:19

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...