Myristoylated Alanine-Rich C Kinase Substrate Accelerates TNF-<i>α</i>-Induced Apoptosis in SH-SY5Y Cells in a Caspases-6 and/or -7-Dependent Manner

Abstract

Cell proliferation, differentiation, and the elimination of unnecessary cells by apoptosis occur in the development of the nervous system. It is reported that brain dysplasia appears as the results of myristoylated alanine-rich C kinase substrate (MARCKS) knockout or the mutant mouse. We therefore expect that MARCKS participates in the development of the nervous system. However, the mechanism underlying such participation has not been identified. In this study, we observed the effects of the overexpression of MARCKS or unphosphorylatable MARCKS on cell proliferation and TNF-α-induced apoptosis in neuroblastoma SH-SY5Y cells. Furthermore, we restrained MARCKS expression by the RNAi method. In the results, MARCKS-overexpressing cells and not unphosphorylatable MARCKS-overexpressing cells showed increased cell proliferation rates. On the other hand, the RNAi decreased the proliferation of MARCKS-knocked down SH-SY5Y cells. These results indicated that MARCKS-overexpressing cells were more sensitive to TNF-α than normal SH-SY5Y cells. Moreover, in MARCKS-overexpressing cells TNF-α-induced apoptosis was inhibited by caspase-6 and -7 inhibitors but not by caspase-3 inhibitor. These results suggested that MARCKS participated in TNF-α-induced apoptosis in a caspase-6 and/or -7-dependent manner.