35 Bcl-2 was the first gene identified as a regulator of apoptosis,36 and subsequently, several bcl-2 homologues were discovered that act as either proapoptotic or antiapoptotic effectors. The present data are in agreement with previous Epigenetics inhibitor observations demonstrating that the overexpression of bcl-2, mcl-1, and bcl-xL37, 38 prevents cells from undergoing apoptosis,

whereas bax, apaf-1, caspase-6, and p53 function to promote cell death.39 Ca buffering also shifted the Bax/Bcl-2 ratio toward the antiapoptotic profile, and this resulted in the accelerated restoration of liver mass after PH. This agrees with recent proteomic data showing that apoptosis pathways are inhibited during liver regeneration.40 Additionally, hepatocyte growth factor, an essential stimulus for liver regeneration, is known to have antiapoptotic activity in injured tissue.41 Similarly, TNF, another initiator of liver regeneration, also

modulates apoptosis in addition to stimulating hepatocyte proliferation.42 Although our results suggest that Ca buffering accelerates liver regeneration by inhibiting apoptosis, an effect on cell proliferation cannot be entirely excluded because Bax/Bcl-2 family proteins regulate liver regeneration independently of their role in modulating apoptosis in the liver.43, 44 Moreover, Ca buffering Selleck BGB324 might also accelerate liver regeneration by modulating ATP production in the mitochondrial matrix because the activity of enzymes of the tricarboxylic acid cycle is regulated by Ca2+.13 Heterologous expression of the Ca2+ binding protein PV has been widely used to study the role of Ca2+ many signaling in the regulation of the cell cycle. PV was targeted to the nucleus or cytoplasm, and with this approach, the role of nuclear Ca2+ in regulating the cell cycle was established in a liver cell

line.9 More recently, PV expression in the cytosol of hepatocytes in vivo demonstrated that cytosolic Ca2+ affects progression through the cell cycle after PH.32 Using PV targeted to the mitochondria, we have now shown that Ca also regulates liver regeneration. Future advances in this field should lead to a better understanding of the ways in which these various Ca2+ compartments act in an integrated manner to regulate liver regeneration. The authors thank Gilson Nogueira for his technical support and Soraya Smaili for antibodies against Bax and Bcl-2 and useful discussions. The authors also thank Dawidson A. Gomes for assistance in the design of the parvalbumin construct. Confocal imaging was supported by CEMEL (Centro de Microscopia Eletrônica, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil). Additional Supporting Information may be found in the online version of this article. “
“Purpose: Allograft hepatitis C is accelerated following liver transplantation (LT). Factors associated with disease progression include viral, demographic, and genetic characteristics of recipients and donors.