Mitochondrial calcium regulates rat liver regeneration through the modulation of apoptosis.

Autor: Guerra MT; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Fonseca EA, Melo FM, Andrade VA, Aguiar CJ, Andrade LM, Pinheiro AC, Casteluber MC, Resende RR, Pinto MC, Fernandes SO, Cardoso VN, Souza-Fagundes EM, Menezes GB, de Paula AM, Nathanson MH, Leite Mde F
Jazyk: angličtina
Zdroj: Hepatology (Baltimore, Md.) [Hepatology] 2011 Jul; Vol. 54 (1), pp. 296-306.
DOI: 10.1002/hep.24367
Abstrakt: Unlabelled: 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.
(Copyright © 2011 American Association for the Study of Liver Diseases.)
Databáze: MEDLINE
Externí odkaz: