MicroRNA profiling in oesophageal adenocarcinoma cell lines and patient serum samples reveals a role for mir-451a in radiation resistance

Many patients with Oesophageal Adenocarcinoma (OAC) do not benefit from chemoradiotherapy treatment due to therapy resistance. To better understand the mechanisms involved in resistance and to find potential biomarkers, we investigated the association of microRNAs, which regulate gene expression, with the response to individual treatments, foc

Over-expression of x-linked inhibitor of apoptosis protein modulates multiple aspects of neuronal Ca2+ signaling

X-linked inhibitor of apoptosis (XIAP) protects and preserves the function of neurons in both in vitro and in vivo models of excitotoxicity. Since calcium (Ca2+) overload is a pivotal event in excitotoxic neuronal cell death, we have determined whether XIAP over-expression influences Ca 2+-signaling in primary cultures of mouse cortical neurons. Using cortical neuron cultures derived from wild-type (Wt) mice transiently transfected with XIAP or from transgenic mice that over-express XIAP, we show that XIAP opposes the rise in intracellular Ca2+ concentration by a variety of triggers. Relative to control neurons, XIAP over-expression produced a slight, but significant, elevation of resting Ca2+ concentrations. By contrast, the rise in intracellular Ca2+ concentrations produced by N-methyl-d-aspartate receptor stimulation and voltage gated Ca2+ channel activation were markedly attenuated by XIAP over-expression. The release of Ca2+ from intracellular stores induced by the sarco/endoplasmic reticulum Ca2+ ATPase inhibitor thapsigargin was also inhibited in neurons transiently transfected with XIAP. The pan-caspase inhibitor zVAD did not, however, diminish the rise in intracellular Ca2+ concentrations elicited by l-glutamate suggesting that XIAP influences Ca2+ signaling in a caspase-independent manner. Taken together, these findings demonstrate that the ability of XIAP to block excessive rises in intracellular Ca2+ by a variety of triggers may contribute to the neuroprotective effects of this anti-apoptotic protein. \ua9 2013 Springer Science+Business Media New York.Peer reviewed: YesNRC publication: Ye