No abstract

␣-Synuclein, an acidic neuronal protein of 140 amino acids, is extremely heat-resistant and is natively unfolded. Recent studies have demonstrated that ␣-synuclein has chaperone activity both in vitro and in vivo, and that this activity is lost upon removing its C-terminal acidic tail. However, the detailed mechanism of the chaperone action of ␣-synuclein remains unknown. In this study, we investigated the molecular mechanism of the chaperone action of ␣-synuclein by analyzing the roles of its N-terminal and C-terminal domains. The N-terminal domain (residues 1-95) was found to bind to substrate proteins to form high molecular weight complexes, whereas the C-terminal acidic tail (residues 96 -140) appears to be primarily involved in solubilizing the high molecular weight complexes. Because the substrate-binding domain and the solubilizing domain for chaperone function are well separated in ␣-synuclein, the N-terminal-binding domain can be substituted by other proteins or peptides. Interestingly, the resultant engineered chaperone proteins appeared to display differential efficiency and specificity in terms of the chaperone function, which depended upon the nature of the binding domain. This finding implies that the C-terminal acidic tail of ␣-synuclein can be fused with other proteins or peptides to engineer synthetic chaperones for specific purposes.

Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high 18F-FDG uptake appear to have more aggressive biological properties than those with low uptake.

Hexokinase type II (HK II) is the key enzyme for maintaining increased glycolysis in cancer cells where it is overexpressed. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, induces cell death in cancer cells. To elucidate the molecular mechanism of 3-BrPA-induced cell death, we used the hepatoma cell lines SNU449 (low expression of HKII) and Hep3B (high expression of HKII). 3-BrPA induced ATP depletion-dependent necrosis and apoptosis in both cell lines. 3-BrPA increased intracellular reactive oxygen species (ROS) leading to mitochondrial dysregulation. NAC (N-acetyl-L: -cysteine), an antioxidant, blocked 3-BrPA-induced ROS production, loss of mitochondrial membrane potential and cell death. 3-BrPA-mediated oxidative stress not only activated poly-ADP-ribose (PAR) but also translocated AIF from the mitochondria to the nucleus. Taken together, 3-BrPA induced ATP depletion-dependent necrosis and apoptosis and mitochondrial dysregulation due to ROS production are involved in 3-BrPA-induced cell death in hepatoma cells.

The distinct feature of hepatitis C virus (HCV) infection is. On the other hand, inhibition of activating receptor expression on NK cell surfaces may also suppress NK cell responses (39). Because they are readily involved in the activation of resting NK cells (5), a reduced display of constitutively expressed activating receptors, such as NKG2D, NKp30, NKp46, DNAM-1, and 2B4, may dampen the functional capacity of NK cells to fight against viral infection. Cytokines secreted in response to HCMV infection indeed inhibit NKG2D expression on the surface of NK cells and limit the ability of NK cells to exert cytotoxicity against target cells (25).The prominent role of NK cells in the innate immune response to virus infection has prompted studies of the NK cell phenotype and functional properties in HCV infection. These include in vitro studies using HCV replicon systems, expression vectors encoding HCV proteins, and recombinant HCV proteins (9,12,24,35,36). For various reasons, these studies yielded contradictory results (12,24,35). It is difficult to interpret interaction between NK cells and HCV-infected cells in noninfectious models, which do not completely simulate the natural life cycle of HCV (19). Ex vivo studies using peripheral blood mononuclear cells (PBMCs) from patients with hepatitis C also showed discrepancies in the functional status of NK cells in HCV infection (1,11,15,26,27,30).Though small-animal models for immunologic research are not readily available yet, recently developed cell culture systems that generate infectious HCV virions in vitro provide more physiological settings in which to study interaction be-* Corresponding author. Mailing address: