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Titolo:
Activation of NF kappa B and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells
Autore:
Murley, JS; Kataoka, Y; Hallahan, DE; Roberts, JC; Grdina, DJ;
Indirizzi:
Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 & Cellular Oncol, Chicago, IL 60637 USA Vanderbilt Univ, Dept Radiat Oncol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 iat Oncol, Nashville, TN 37232 USA Univ Utah, Coll Pharm, Dept Med Chem, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 Chem, Salt Lake City, UT 84112 USA
Titolo Testata:
FREE RADICAL BIOLOGY AND MEDICINE
fascicolo: 12, volume: 30, anno: 2001,
pagine: 1426 - 1439
SICI:
0891-5849(20010615)30:12<1426:AONKBA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; MANGANESE SUPEROXIDE-DISMUTASE; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTORS; REDOX REGULATION; CYTOPROTECTOR AMIFOSTINE; CYCLE PROGRESSION; TNF-ALPHA; WR-1065;
Keywords:
nonprotein thiols; nuclear transcription factor kappa B; manganese superoxide dismutase; intercellular adhesion molecule-1; gene expression; free radicals;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Grdina, DJ Univ Chicago, Dept Radiat & Cellular Oncol, MC1105,Rm E-SB-11B,5841 S Maryland Ave, Chicago, IL 60637 USA Univ Chicago MC1105,Rm E-SB-11B,5841 S Maryland Ave Chicago IL USA 60637
Citazione:
J.S. Murley et al., "Activation of NF kappa B and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells", FREE RAD B, 30(12), 2001, pp. 1426-1439

Abstract

The effect of nonprotein thiol (NPT) free radical scavengers WR-1065 (SH) and WR-33278 (SS), the active thiol and disulfide metabolites of amifostine, N-acetylcysteine (NAC; both L- and D- isomers), mesna, captopril, and dithiothreitol (DTT) on NF kappaB activation in human microvascular endothelial cells (HMEC) was investigated and contrasted to TNF alpha. The use of each of these NPTs at millimolar concentrations independent of oxidative damage-inducing agents resulted in a marked activation of NF kappaB, with the maximum effect observed between 30 min and 1 h after treatment. Only the SH and SS forms of amifostine, however. were effective in activating NF kappaB when administered at micromolar levels. Using a supershift assay, SH and SSequally affected the p50-p65 heterodimer, but not homodimers or heterodimers containing p52 or c-Rel subunits of NF kappaB. Neither catalase nor pyruvate when added to the culture medium to minimize hydrogen peroxide production had an effect on NF kappaB activation by SH. Thus, while oxidative damage is known to activate NF kappaB, the intracellular redox environment may also be affected by the addition of free radical scavenging agents such as NPT, and these in turn are capable of activating the redox sensitive transcription factor NF kappaB. There does not appear to be a significant role, if any, for the production of H2O2 as an intermediate step in the activationof NF kappaB by either the SH or the SS form of amifostine. Rather, the underlying mechanism of action, especially for the SS form, may be related tothe close structural and functional similarities of these agents to polyamines, which have been reported to be capable of activating NF kappaB. In contrast to TNF alpha, exposure of cells to either 40 muM or 4 mM of SH for 30 min did not induce intercellular adhesion molecule-1 (ICAM-1) gene expression, but did increase manganese superoxide dismutase (MnSOD) gene expression. MnSOD expression rose by 2-fold and remained elevated from 4 to 22 h following SH exposure. (C) 2001 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:12:44