| Toxoplasma gondii infection inhibits the mitochondrial apoptosis through induction of Bcl-2 and HSP70. | |
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MedLine Citation:
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PMID: 20680337 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Heat-shock protein 70 (HSP70) is highly expressed in Toxoplasma gondii-infected cells. However, the role of this protein is not well understood, especially during apoptosis. This study addresses the mechanism behind the antiapoptotic chaperone activity of HSP70 in Toxoplasma-infected host cells using a human macrophage cell line, THP-1 by Western blot, DNA fragmentation assay, immunoprecipitation, and a caspase-3/7 activity assay based on cleavage of the colorimetric substrate DEVD-pNA. Apoptosis induced by arsenic trioxide (As(2)O(3)) was inhibited in T. gondii-infected THP-1 cells, but not in uninfected cells. Without As(2)O(3) induction of apoptosis, T. gondii infection caused increased expression of Bcl-2 and HSP70, but not caspase-3. However, active form caspase-3 levels were lower in As(2)O(3)-treated infected cells as compared with As(2)O(3)-treated uninfected cells. Bcl-2 expression in As(2)O(3)-treated infected cells was similar to that in cells infected with T. gondii. Translocation of apoptosis-inducing factor (AIF) and release of cytochrome c from mitochondria were inhibited in As(2)O(3)-treated infected cells as compared with As(2)O(3)-treated uninfected cells. Increased parasite loads in Toxoplasma-infected macrophages caused higher HSP70 and Bcl-2 expression in whole-cell extracts and fractionated components, respectively. However, expression of AIF and cytochrome c was unaffected. Toxoplasma dose-dependently inhibited caspase-3 activation, thus revealing an anti-apoptotic parasite activity on cytochrome c-mediated caspase activation in subcellular components. In addition, immunoprecipitation analysis suggested that HSP70 is capable of binding to the pro-apoptotic factors AIF and Apaf-1, but not to cytochrome c or procaspase-9. Taken together, these data demonstrate that T. gondii infection inhibits mitochondrial apoptosis through overproduction of anti-apoptotic Bcl-2 as well as HSP70, which are increased parasite loads dependently. |
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Authors:
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Il-Young Hwang; Juan Hua Quan; Myoung-Hee Ahn; Hassan Ahmed Hassan Ahmed; Guang-Ho Cha; Dae-Whan Shin; Young-Ha Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-03 |
Journal Detail:
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Title: Parasitology research Volume: 107 ISSN: 1432-1955 ISO Abbreviation: Parasitol. Res. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-09 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8703571 Medline TA: Parasitol Res Country: Germany |
Other Details:
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Languages: eng Pagination: 1313-21 Citation Subset: IM |
Affiliation:
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Department of Infection Biology, Research Institute for Medical Science, Chungnam National University School of Medicine, 6 Munhwa-dong, Jung-gu, Daejeon, 301-131, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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