A number of reports have focused on potential signaling roles of nSMase1. Some studies have suggested that nSMase1 is important for ceramide generation in response to stress. For example, in the T cell hybridoma (3DO) cells, specific inhibition of nSMase1 by antisense RNA reduced T cell receptor mediated apoptosis (Tonnetti et al., 1999) and inhibition of nSMase1 decreased ceramide levels, IL-2 production, and MAPK activation during the T-cell receptor response. Thus, nSMase1-derived ceramide may be an important component of the T cell receptor signaling machinery. Additionally, in zebrafish embryonic cells, the inhibition of nSMase1 by an antisense oligonucleotide repressed the induction of ceramide generation, caspase-3 activation, and apoptotic cell death induced by heat stress (Yabu et al., 2008).
