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- Title
Identification of prothymosin-α 1, the necrosis-apoptosis switch molecule in cortical neuronal cultures.
- Authors
Ueda, Hiroshi; Fujita, Ryousuke; Yoshida, Akira; Matsunaga, Hayato; Ueda, Mutsumi
- Abstract
We initially identified a nuclear protein, prothymosin-α 1(ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProToα 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[sub 2]-family proteins. The apoptosis caused by ProTα was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTα-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 PKCβ[sub II] expression prevented this cell death mode switch. Collectively, these results suggest that ProTα 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.
- Subjects
APOPTOSIS; NECROSIS; NEURONS; ADENOSINE triphosphate; CELL death
- Publication
Journal of Cell Biology, 2007, Vol 176, Issue 6, p853
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200608022