Elk-1 belongs to the ternary complex factors (TCFs) subfamily of the ETS domain proteins, and plays a critical role in the expression of immediate-early genes (IEGs) upon mitogen stimulation and activation of the mitogen-activated protein kinase (MAPK) cascade. The association of TCFs with serum response elements (SREs) on IEG promoters has been widely studied and a role for Elk-1 in promoting cell cycle entry has been determined. However, the presence of the ETS domain transcription factor Elk-1 in axons and dendrites of post-mitotic adult brain neurons has implications for an alternative function for Elk-1 in neurons other than controlling proliferation. In this study, possible alternative roles for Elk-1 in neurons were investigated, and it was demonstrated that blocking TCF-mediated transactivation in neuronal cells leads to apoptosis through a caspase-dependent mechanism. Indeed RNAi-mediated depletion of endogenous Elk-1 results in increased caspase activity. Conversely, overexpression of either Elk-1 or Elk-VP16 fusion proteins was shown to rescue PC12 cells from chemically-induced apoptosis, and that higher levels of endogenous Elk-1 correlated with longer survival of DRGs in culture. It was shown that Elk-1 regulated the Mcl-1 gene expression required for survival, and that RNAi-mediated degradation of endogenous Elk-1 resulted in elimination of the mcl-1 message. We have further identified the survival-of-motor neuron-1 (SMN1) gene as a novel target of Elk-1, and show that the ets motifs in the SMN1 promoter are involved in this regulation.
Our results support the notion that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis and occurrence of neurological symptoms.
With the development of gold nanorods (AuNRs) for a number of biomedical applications, understanding their various biological effects has become important. Surface functionalization of AuNRs is attracting increasing attention with regard to toxicity, cellular uptake, localization, therapeutic potential, and biodistribution. The aim of the study is to synthesis of stable AuNRs functionalized with polyethylenimine (PEI) and polyethylene glycol (PEG), multiparametric investigation of their cellular effects on the dorsal root ganglion (DRG) primary sensory neurones, evaluation of the in vitro/in vivo biodistribution, and toxicity. PEI and PEG surface coatings increased both biocompatibility and biodistribution of the AuNRs. With the near‐infrared laser of the two‐photon microscope, very strong radiations are taken from the nucleolus parts of the neurones particularly and these localizations of the AuNRs‐PEI are confirmed by the transmission electron microscope images. Inductively coupled plasma mass spectrometry analysis shows the presence of AuNRs in liver, spleen, kidney, heart, blood, and brain within a 30 day period. It is observed that the surface coatings of the AuNRs significantly increase the biodistribution and biocompatibility. The surface functionalization, stability, and biocompatibility of the AuNRs are very important parameters for the potential nanotheranostic applications of AuNRs in the next studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.