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Identification of prothymosin-
1, the necrosisapoptosis switch molecule in cortical neuronal cultures
Correspondence to Hiroshi Ueda: ueda{at}nagasaki-u.ac.jp
We initially identified a nuclear protein, prothymosin-
1 (ProT
), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProT
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 Bcl2-family proteins. The apoptosis caused by ProT
was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProT
-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 PKCßII expression prevented this cell death mode switch. Collectively, these results suggest that ProT
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.
, prothymosin-
1.
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