| Mechanism of beta 2-microglobulin-induced apoptosis in the K562 leukemia cell line, defective in major histocompatibility class 1. | |
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MedLine Citation:
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PMID: 12529972 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: It has been shown that exogenous beta 2-microglobulin (beta 2m) triggers significant apoptosis in several cell lines, but the molecular mechanism of beta 2m-induced apoptosis remains to be found. MATERIALS AND METHODS: To understand the mechanism of beta 2m-induced apoptosis, we added purified human beta 2m to cultures of K562 human chronic myelocytic leukemia cells, detected apoptosis by DNA fragmentation and annexin V binding assays, measured mitochondrial membrane potential (delta psi m), and used Z-VAD-fmk, a general inhibitor of caspases, inhibitors of caspases-1 and-3, as well as Western blot analysis to detect activated caspases. RESULTS: beta 2m-induced apoptosis was associated with decreased delta psi m K562 cells. Treatment with the general caspase inhibitor Z-VAD-fmk, as well as the caspase-1 inhibitor YVAD-CHO, significantly blocked beta 2m-induced apoptosis. However, Western blot analysis revealed that caspase-1 was intrinsically activated in untreated as well as beta 2m-treated K562 cells. Furthermore, beta 2m-induced apoptosis was not associated with the cleavage of caspase-3 as revealed by Western blot analysis, but was inhibited by an inhibitor of caspase-3, Z-DEVD-CHO, suggesting that not caspase-3, but a caspase-3-like enzyme may be involved in beta 2m-induced apoptosis. Western blot analysis also revealed that caspases-4, -8 and -9 were not activated during beta 2m-induced apoptosis in these cells. CONCLUSION: These results reveal that beta 2m-induced apoptosis in K562 cells occurs by a mechanism dependent on decreased mitochondrial delta psi m. Moreover, while caspase-1 activity may be one of the factors involved in beta 2m-induced apoptosis, activation of this caspase alone does not cause apoptosis, and other proapoptotic factors including activation of a caspase-3-like enzyme, independently of caspases-4, -8 and -9 activity, may be required to trigger apoptosis. |
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Authors:
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Ching-Huang Wu; John D Gordon; Xiaoling Zhong; Ahmad R Safa |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Anticancer research Volume: 22 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 2002 Sep-Oct |
Date Detail:
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Created Date: 2003-01-17 Completed Date: 2003-02-20 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 2613-21 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology and Indiana University Cancer Center, 1044 West Walnut R4-119, Indianapolis, IN 46202, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects*,
immunology,
physiology Caspase 1 / antagonists & inhibitors, metabolism Caspase 3 Caspases / antagonists & inhibitors, metabolism Cell Division / drug effects Cytochrome c Group / secretion HLA Antigens / biosynthesis*, immunology Humans Intracellular Membranes / drug effects, physiology K562 Cells / cytology, drug effects*, enzymology, immunology Membrane Potentials / drug effects, physiology Mitochondria / drug effects, physiology beta 2-Microglobulin / antagonists & inhibitors, immunology, pharmacology*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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CA 80734/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytochrome c Group; 0/HLA Antigens; 0/beta 2-Microglobulin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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