| Titanium dioxide nanoparticles induce apoptosis through the JNK/p38-caspase-8-Bid pathway in phytohemagglutinin-stimulated human lymphocytes. | |
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MedLine Citation:
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PMID: 19555659 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the signaling pathways underlying nano-TiO(2)-induced apoptosis in cultured human lymphocytes. Nano-TiO(2) increased the proportion of sub-G1 cells, activated caspase-9 and caspase-3, and induced caspase-3-mediated PARP cleavage. Nano-TiO(2) also induced loss of mitochondrial membrane potential, which suggests that nano-TiO(2) induces apoptosis via a mitochondrial pathway. A time-sequence analysis of the induction of apoptosis by nano-TiO(2) revealed that nano-TiO(2) triggered apoptosis through caspase-8/Bid activation. We also observed that inhibition of caspase-8 by z-IETD-fmk suppressed the caspase-8/Bid activation, caspase-3-mediated PARP cleavage, and apoptosis. Nano-TiO(2) activated two MAPKs, p38 and JNK. In addition, the selective p38 inhibitor SB203580 and selective JNK inhibitor SP600125 suppressed nano-TiO(2)-induced apoptosis and caspase-8 activation to moderate and significant extents, respectively. Knockdown of protein levels of JNK1 and p38 using an RNA interference technique also suppressed caspase-8 activation. Our results suggest that nano-TiO(2)-induced apoptosis is mediated by the p38/JNK pathway and the caspase-8-dependent Bid pathway in human lymphocytes. |
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Authors:
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Su Jin Kang; Byeong Mo Kim; Young Joon Lee; Sung Hee Hong; Hai Won Chung |
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Publication Detail:
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Type: Journal Article Date: 2009-06-23 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 386 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-07-21 Completed Date: 2009-08-11 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 682-7 Citation Subset: IM |
Affiliation:
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School of Public Health and Institute of Health and Environment, Seoul National University, 28 Yunkeun-dong, Chongno-ku, Seoul 110-460, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis* BH3 Interacting Domain Death Agonist Protein / metabolism Caspase 8 / antagonists & inhibitors, metabolism Cells, Cultured Cysteine Proteinase Inhibitors / pharmacology Humans Lymphocyte Activation / drug effects* Lymphocytes / drug effects, metabolism, physiology MAP Kinase Kinase 4 / antagonists & inhibitors, metabolism Nanoparticles* Oligopeptides / pharmacology Phytohemagglutinins / pharmacology Titanium / pharmacology* p38 Mitogen-Activated Protein Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
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0/BH3 Interacting Domain Death Agonist Protein; 0/Cysteine Proteinase Inhibitors; 0/Oligopeptides; 0/Phytohemagglutinins; 0/benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; 13463-67-7/titanium dioxide; 7440-32-6/Titanium; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 4; EC 3.4.22.-/Caspase 8 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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