| Mitochondrial calcium regulates rat liver regeneration through the modulation of apoptosis. | |
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MedLine Citation:
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PMID: 21503946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Subcellular Ca(2+) signals control a variety of responses in the liver. For example, mitochondrial Ca(2+) (Ca(mit)(2+)) regulates apoptosis, whereas Ca(2+) in the nucleus regulates cell proliferation. Because apoptosis and cell growth can be related, we investigated whether Ca(mit)(2+) also affects liver regeneration. The Ca(2+)-buffering protein parvalbumin, which was targeted to the mitochondrial matrix and fused to green fluorescent protein, was expressed in the SKHep1 liver cell line; the vector was called parvalbumin-mitochondrial targeting sequence-green fluorescent protein (PV-MITO-GFP). This construct properly localized to and effectively buffered Ca(2+) signals in the mitochondrial matrix. Additionally, the expression of PV-MITO-GFP reduced apoptosis induced by both intrinsic and extrinsic pathways. The reduction in cell death correlated with the increased expression of antiapoptotic genes [B cell lymphoma 2 (bcl-2), myeloid cell leukemia 1, and B cell lymphoma extra large] and with the decreased expression of proapoptotic genes [p53, B cell lymphoma 2-associated X protein (bax), apoptotic peptidase activating factor 1, and caspase-6]. PV-MITO-GFP was also expressed in hepatocytes in vivo with an adenoviral delivery system. Ca(mit)(2+) buffering in hepatocytes accelerated liver regeneration after partial hepatectomy, and this effect was associated with the increased expression of bcl-2 and the decreased expression of bax. CONCLUSION: Together, these results reveal an essential role for Ca(mit)(2+) in hepatocyte proliferation and liver regeneration, which may be mediated by the regulation of apoptosis. |
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Authors:
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Mateus T Guerra; Emerson A Fonseca; Flavia M Melo; Viviane A Andrade; Carla J Aguiar; Lídia M Andrade; Ana Cristina N Pinheiro; Marisa C F Casteluber; Rodrigo R Resende; Mauro C X Pinto; Simone O A Fernandes; Valbert N Cardoso; Elaine M Souza-Fagundes; Gustavo B Menezes; Ana M de Paula; Michael H Nathanson; Maria de Fátima Leite |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 54 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-28 Completed Date: 2011-09-30 Revised Date: 2012-03-12 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 296-306 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
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Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology* Calcium / metabolism* Calcium Signaling / physiology Cell Proliferation Liver Regeneration / physiology* Male Mitochondria, Liver / metabolism* Models, Animal Proto-Oncogene Proteins c-bcl-2 / metabolism Rats Rats, Sprague-Dawley bcl-2-Associated X Protein / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK34989/DK/NIDDK NIH HHS; DK45710/DK/NIDDK NIH HHS; DK57751/DK/NIDDK NIH HHS; P01 DK057751-10/DK/NIDDK NIH HHS; P30 DK034989-25S1/DK/NIDDK NIH HHS; R01 DK045710-10/DK/NIDDK NIH HHS; R01 DK045710-18/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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