Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/59684
Type
ArticleCopyright
Restricted access
Embargo date
2099-12-31
Collections
Metadata
Show full item record
MITOCHONDRIAL CALCIUM REGULATES RAT LIVER REGENERATION THROUGH THE MODULATION OF APOPTOSIS
Author
Guerra, Mateus Tavares
Fonseca, Emerson A.
Melo, Flavia M.
Andrade, V. A
Aguiar, Carla J.
Andrade, Lídia Maria
Pinheiro, Ana Cristina N.
Casteluber, Marisa F.
Resende, Rodrigo R.
Pinto, Mauro C. X.
Fernandes, Simone O. A.
Cardoso, Valbert N.
Fagundes, Elaine Maria Souza
Menezes, Gustavo B.
Paula, Ana M. de
Nathanson, Michael H.
Leite, Maria de Fatima
Fonseca, Emerson A.
Melo, Flavia M.
Andrade, V. A
Aguiar, Carla J.
Andrade, Lídia Maria
Pinheiro, Ana Cristina N.
Casteluber, Marisa F.
Resende, Rodrigo R.
Pinto, Mauro C. X.
Fernandes, Simone O. A.
Cardoso, Valbert N.
Fagundes, Elaine Maria Souza
Menezes, Gustavo B.
Paula, Ana M. de
Nathanson, Michael H.
Leite, Maria de Fatima
Affilliation
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Section of Digestive Diseases. Department of Internal Medicine. Yale University School of Medicine. New Haven, CT, USA
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Izabela Hendrix Metodist Institute. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/René Rachou Research Center. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Nanobiotechnology Laboratory. Federal University of São João del Rei. São João del Rei, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Radioisotope Laboratory. Department of Clinical and Toxicological Analysis. Faculty of Pharmacy. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Radioisotope Laboratory. Department of Clinical and Toxicological Analysis. Faculty of Pharmacy. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Section of Digestive Diseases. Department of Internal Medicine. Yale University School of Medicine. New Haven, CT, USA
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Howard Hughes Medical Institute.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Izabela Hendrix Metodist Institute. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/René Rachou Research Center. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Nanobiotechnology Laboratory. Federal University of São João del Rei. São João del Rei, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Radioisotope Laboratory. Department of Clinical and Toxicological Analysis. Faculty of Pharmacy. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Radioisotope Laboratory. Department of Clinical and Toxicological Analysis. Faculty of Pharmacy. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Section of Digestive Diseases. Department of Internal Medicine. Yale University School of Medicine. New Haven, CT, USA
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Howard Hughes Medical Institute.
Abstract
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. (HEPATOLOGY 2011;54:296-306
Share