Affymetrix microarray analysis of the effects of isonicotinamide on HEK293 cells

ABSTRACT: Sirtuin deacetylases and forkhead box class O (FOXO) transcription factors are central regulators of cell survival, cell cycle and cellular resistance to stress in response to signals from hormones, growth factors and oxidative stress. FOXO activity is modulated by the sirtuins, which function in a NAD+-dependent manner. Sirtuin activity, on the other hand is subject to inhibition by a natural compound nicotinamide (NAM). This study aims to investigate the effects of NAM on the sirtuin pathway and cellular homeostasis. It was hypothesized that NAM inhibits the sirtuin deacetylase activity, which then shifts FOXO-dependent responses away from stress resistance and towards apoptosis. Expression analysis using Affymetrix microarray was employed to determine differential gene expression in HEK293 cells in response to NAM treatment. Data analyses were performed using multiple algorithms, computational methods and interaction analyses. Significant changes in gene expression were detected with the generation of an expansive list of genes and interaction amongst gene groups were identified from the NAM treatment at different concentration. Substantial changes in expression profiles were detected for genes involved in a number of unique cellular pathways and functions, including cell cycle arrest, cellular proliferation and differentiation, metabolism, apoptotic signaling, inflammatory regulation and various disease conditions such as cancer. In addition, this study observed that sirtuin activities exhibit complex cell- and contextdependent behavior in modulating FOXO signaling. Contrasting roles of FOXOs and sirtuins appear to have opposite effects on cellular homeostasis. In addition, the coexistence of reciprocal regulations in this cell system suggested several levels of feedback control and illustrated the complexity of an existing fine-tuned regulatory network system between these two proteins. Future work aims to characterize putative regulators and effectors of sirtuin- and FOXO-related pathways using molecular approaches such and RNA interference knockdown of individual FOXO-isoforms. Inter-connectivity of the pathways will provide invaluable insight into current understanding of cell degeneration diseases such as diabetes, cancers and neurological disorders. Keywords: Serial concentration experiment

ORGANISM(S): Homo sapiens

PROVIDER: GSE9707 | GEO | 2018/12/31

REPOSITORIES: GEO