Sensitization of vascular smooth muscle cell to TNF-α-mediated death in the presence of palmitate

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dc.contributor.authorMun Chual Rho-
dc.contributor.authorK A Lee-
dc.contributor.authorS M Kim-
dc.contributor.authorC S Lee-
dc.contributor.authorM J Jang-
dc.contributor.authorYoung Kook Kim-
dc.contributor.authorHyun Sun Lee-
dc.contributor.authorY H Choi-
dc.contributor.authorB Y Rhim-
dc.contributor.authorK Kim-
dc.date.accessioned2017-04-19T09:07:06Z-
dc.date.available2017-04-19T09:07:06Z-
dc.date.issued2007-
dc.identifier.issn0041-008X-
dc.identifier.uri10.1016/j.taap.2007.02.008ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/7912-
dc.description.abstractSaturated free fatty acids (FFAs), including palmitate, can activate the intrinsic death pathway in cells. However, the relationship between FFAs and receptor-mediated death pathway is still unknown. In this study, we have investigated whether FFAs are able to trigger receptor-mediated death. In addition, to clarify the mechanisms responsible for the activation, we examined the biochemical changes in dying vascular smooth muscle cell (VSMC) and the effects of various molecules to the receptor-mediated VSMC death. Tumor necrosis factor (TNF)-α-mediated VSMC death occurred in the presence of sub-cytotoxic concentration of palmitate as determined by assessing viability and DNA degradation, while the cytokine did not influence VSMC viability in the presence of oleate. The VSMC death was inhibited by the gene transfer of a dominant-negative Fas-associated death domain-containing protein and the baculovirus p35, but not by the bcl-xL or the c-Jun N-terminal kinase (JNK) binding domain of JNK-interacting protein-1, in tests utilizing recombinant adenoviruses. The VSMC death was also inhibited by a neutralizing anti-TNF receptor 1 antibody, the caspase inhibitor z-VAD, and the cathepsin B inhibitor CA074, a finding indicative of the role of both caspases and cathepsin B in this process. Consistent with this finding, caspase-3 activation and an increase in cytosolic cathepsin B activity were detected in the dying VSMC. Palmitate inhibited an increase of TNF-α-mediated nuclear factor kappa B (NF-κB) activity, the survival pathway activated by the cytokine, by hindering the translocation of the NF-κB subunit of p65 from the cytosol into the nucleus. The gene transfer of inhibitor of NF-κB predisposed VSMC to palmitate-induced cell death. To the best of our knowledge, this study is the first report to demonstrate the activation of TNF-α-mediated cell death in the presence of palmitate. The current study proposes that FFAs would take part in deleterious vascular consequences of such patients with elevated levels of FFAs as diabetics and obese individuals via the triggering of receptor-mediated death pathways of VSMC.-
dc.publisherElsevier-
dc.titleSensitization of vascular smooth muscle cell to TNF-α-mediated death in the presence of palmitate-
dc.title.alternativeSensitization of vascular smooth muscle cell to TNF-α-mediated death in the presence of palmitate-
dc.typeArticle-
dc.citation.titleToxicology and Applied Pharmacology-
dc.citation.number3-
dc.citation.endPage319-
dc.citation.startPage311-
dc.citation.volume220-
dc.contributor.affiliatedAuthorMun Chual Rho-
dc.contributor.affiliatedAuthorYoung Kook Kim-
dc.contributor.affiliatedAuthorHyun Sun Lee-
dc.contributor.alternativeName노문철-
dc.contributor.alternativeName이경아-
dc.contributor.alternativeName김선미-
dc.contributor.alternativeName이창식-
dc.contributor.alternativeName장민정-
dc.contributor.alternativeName김영국-
dc.contributor.alternativeName이현선-
dc.contributor.alternativeName최영현-
dc.contributor.alternativeName임병용-
dc.contributor.alternativeName김관회-
dc.identifier.bibliographicCitationToxicology and Applied Pharmacology, vol. 220, no. 3, pp. 311-319-
dc.identifier.doi10.1016/j.taap.2007.02.008-
dc.subject.keywordapoptosis-
dc.subject.keywordpalmitate-
dc.subject.keywordtumor necrosis factor-
dc.subject.keywordvascular smooth muscle cell-
dc.subject.localapoptosis-
dc.subject.localApoptosis-
dc.subject.localpalmitate-
dc.subject.localPalmitates-
dc.subject.localtumor necrosis factor-
dc.subject.localTumor necrosis factor-
dc.subject.localtumor necrosis factor--
dc.subject.localVascular smooth muscle cell-
dc.subject.localvascular smooth muscle cell-
dc.description.journalClassY-
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
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