Delay in Apoptosome Formation Attenuates Apoptosis in mouse Embryonic Stem Cell Differentiation [Bioenergetics]

April 22nd, 2014 by Akbari-Birgani, S., Hosseinkhani, S., Mollamohamadi, S., Baharvand, H.

Differentiation is an inseparable process of development in multicellular organisms. Mouse embryonic stem cells (mESCs) represent a valuable research tool to conduct in vitro studies of cell differentiation. Apoptosis as a well-known cell death mechanism shows some common features with cell differentiation which has caused a number of ambiguities in the field. The research question here is how cells could differentiate these two processes from each other. We have investigated the role of mitochondrial apoptotic pathway and cell energy level during differentiation of mESCs into the cardiomyocytes and their apoptosis. p53 expression, Cytochrome c release, apoptosome formation and caspase-3/7 activation are observed upon induction of both apoptosis and differentiation. However, remarkable differences are detected in time of cytochrome c appearance, apoptosome formation and caspase activity upon induction of both processes. In apoptosis, apoptosome formation and caspase activity was observed rapidly following the cytochrome c release. Unlike apoptosis, the release of cytochrome c upon differentiation took more time and the maximum caspase activity was also postponed for 24h.This delay is suggesting that there is regulatory mechanism during mESCs differentiation into cardiomyocytes. The highest ATP content of cells was observed immediately after cytochrome c release at 6h upon apoptosis induction and then decreased but it was gradually increased up to 48 h upon differentiation. These observations suggest that delay in release of cytochrome c and rise in ATP content of cells attenuate apoptosome formation and caspase activation thereby discriminates apoptosis from differentiation in mESCs.