Publikationsdatum:
1992-03-13
Beschreibung:
Tumor necrosis factor-alpha (TNF, cachectin), a protein secreted by activated macrophages, participates in inflammatory responses and in infectious and neoplastic disease states. The mechanisms by which TNF exerts cytotoxic, hormonal, and other specific effects are obscure. Structural studies of the TNF trimer have revealed a central pore-like region. Although several amino acid side chains appear to preclude an open channel, the ability of TNF to insert into lipid vesicles raised the possibility that opening might occur in a bilayer milieu. Acidification of TNF promoted conformational changes concordant with increased surface hydrophobicity and membrane insertion. Furthermore, TNF formed pH-dependent, voltage-dependent, ion-permeable channels in planar lipid bilayer membranes and increased the sodium permeability of human U937 histiocytic lymphoma cells. Thus, some of the physiological effects of TNF may be elicited through its intrinsic ion channel-forming activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kagan, B L -- Baldwin, R L -- Munoz, D -- Wisnieski, B J -- 2 T32 HL07386/HL/NHLBI NIH HHS/ -- GM22240/GM/NIGMS NIH HHS/ -- MH43433/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 13;255(5050):1427-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, School of Medicine, University of California, Los Angeles 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1371890" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Cell Membrane Permeability/drug effects
;
Electrochemistry
;
Humans
;
Hydrogen-Ion Concentration
;
Ion Channels/*drug effects
;
Lipid Bilayers/chemistry
;
Recombinant Proteins/pharmacology
;
Sodium Channels/drug effects
;
Tumor Cells, Cultured/drug effects
;
Tumor Necrosis Factor-alpha/*pharmacology
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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