Mitochondrially targeted Bcl-2 and Bcl-X(L) chimeras elicit different apoptotic responses.

The Bcl-2 family of proteins interacts at the mitochondria to regulate apoptosis. However, the anti-apoptotic Bcl-2 and Bcl-X(L) are not completely localized to the mitochondria. In an attempt to generate Bcl-2 and Bcl-X(L) chimeras that are constitutively localized to the mitochondria, we substituted their C-terminal transmembrane tail or both the C-terminal transmembrane tail and the adjacent loop with the equivalent regions from Bak or Bax mutant (BaxS184V) as these regions determine the mitochondrial localization of Bak and Bax. The effects of these substitutions on subcellular localization and their activities were assessed following expression in HeLa and CHO K1 cells. The substitution of the C-terminal tail or the C-terminal tail and the adjacent loop of Bcl-2 with the equivalent regions from Bak or the Bax mutant resulted in its association with the mitochondria. This change in subcellular localization of Bcl-2 chimeras triggered cells to undergo apoptotic-like cell death. The localization of this Bcl-2 chimera to the mitochondria may be associated with the disruption of mitochondrial membrane potential. Unlike Bcl-2, the loop structure adjacent to the C-terminal tail in Bcl-X(L) is crucial for its localization. To localize the Bcl-X(L) chimeras to the mitochondria, the loop structure next to the C-terminal tail in Bcl-X(L) protein must remain intact and cannot be substituted by the loop from Bax or Bak. The chimeric Bcl-X(L) with both its C-terminal tail and the loop structure replaced by the equivalent regions of Bak or Bax mutant localized throughout the entire cytosol. The Bcl-X(L) chimeras that are targeted to the mitochondria and the wild type Bcl-X(L) provided same protection against cell death under several death inducing conditions.

Fabrications of hollow nanocubes of Cu(2)O and Cu via reductive self-assembly of CuO nanocrystals.

In this work, a template-free synthetic approach for generating single-crystalline hollow nanostructures has been described. Using the small optical band-gap cuprous oxide Cu(2)O as a model case, we demonstrate that, instead of normally known spherical aggregates, primary nanocrystalline particles can first self-aggregate into porous organized solids with a well-defined polyhedral shape according to the oriented attachment mechanism, during which chemical conversion can also be introduced. In contrast to the spherical aggregates, where the nanocrystallites are randomly joined together, the Cu(2)O nanocrystallites in the present case are well organized, maintaining a definite geometric shape and a global crystal symmetry. Due to the presence of intercrystallite space, hollowing and chemical conversion can also be carried out in order to create central space and change the chemical phase of nanostructured polyhedrons. It has been revealed that Ostwald ripening plays a key role in the solid evacuation process. Using this synthetic strategy, we have successfully prepared single-crystal-like Cu(2)O nanocubes and polycrystalline Cu nanocubes with hollow interiors. For the first time, we demonstrate that nanostructured polyhedrons of functional materials with desired interiors can be synthesized in solution via a combination of oriented attachment and Ostwald ripening processes.

Formation of colloidal CuO nanocrystallites and their spherical aggregation and reductive transformation to hollow Cu2O nanospheres.

In this work, we demonstrate that cuprous oxide Cu(2)O nanospheres with hollow interiors can be fabricated from a reductive conversion of aggregated CuO nanocrystallites without using templates. A detailed process mechanism has been revealed: (i) formation of CuO nanocrystallites; (ii) spherical aggregation of primary CuO crystallites; (iii) reductive conversion of CuO to Cu(2)O; and (iv) crystal aging and hollowing of Cu(2)O nanospheres. In this template-free process, Ostwald ripening is operative in (iv) for controlling crystallite size in shell structures and thus for precisely tuning the optical band gap energy (E(g)) of resultant semiconductor nanostructures. For the first time, a wealth of colorful Cu(2)O hollow nanospheres (outer diameters in 100-200 nm), with variable E(g) in the range of 2.405-2.170 eV, has been fabricated via this novel chemical route. Considering their unique hollow structure and facile tuning in band gap energy, the prepared Cu(2)O hollow spheres can be potentially useful for harvesting solar energy in the visible range. Possibility of fabrication of Cu-Cu(2)O nanocomposites has also been discussed.