Identification of prothymosin-α1, the necrosis-apoptosis switch molecule in cortical neuronal cultures

We initially identified a nuclear protein, prothymosin-alpha 1 (ProT alpha), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProT alpha inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl(2)-family proteins. The apoptosis caused by ProT alpha was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProT alpha-induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKC beta(II) expression prevented this cell death mode switch. Collectively, these results suggest that ProT alpha is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors.