Expression and Subcellular Localization of a Novel Nuclear Acetylcholinesterase Protein

Abstract

Acetylcholine is found in the nervous system and also in other cell types (endothelium, lymphocytes, and epithelial and blood cells), which are globally termed the non-neuronal cholinergic system. In this study we investigated the expression and subcellular localization of acetylcholinesterase (AChE) in endothelial cells. Our results show the expression of the 70-kDa AChE in both cytoplasmic and nuclear compartments. We also describe, for the first time, a nuclear and cytoskeleton-bound AChE isoform with ϳ55 kDa detected in endothelial cells. This novel isoform is decreased in response to vascular endothelial growth factor via the proteosomes pathway, and it is down-regulated in human leukemic T-cells as compared with normal T-cells, suggesting that the decreased expression of the 55-kDa AChE protein may contribute to an angiogenic response and associate with tumorigenesis. Importantly, we show that its nuclear expression is not endothelial cell-specific but also evidenced in non-neuronal and neuronal cells. Concerning neuronal cells, we can distinguish an exclusively nuclear expression in postnatal neurons in contrast to a cytoplasmic and nuclear expression in embryonic neurons, suggesting that the cell compartmentalization of this new AChE isoform is changed during the development of nervous system. Overall, our studies suggest that the 55-kDa AChE may be involved in different biological processes such as neural development, tumor progression, and angiogenesis.

The Ubiquity Nature of Acetylcholine

“…The molecular form of 70 kDa is also expressed at cytoplasm and nuclear compartments, where the latter also expressed an AChE isoform with approximately 55 kDa [11]. We verified that the nuclear expression is not endothelial cell-specific but is also evidenced in nonneuronal and neuronal cells [11].…”

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

“…In parallel to the definitive findings established for R-AChE [61], [65], evidence is only now accumulating that the C-terminal domain of T-AChE may also undergo proteolytic cleavage in vivo [41], [66]–[69]. This helical domain independently exhibits autonomous bioactivity comparable to many of the non-catalytic effects attributed to the intact T-isoform of AChE [29]–[31], [33], [35], [39], [61], [66], [70].…”

“…Certainly a number of transcription factors contain such motifs [89], most notably those involved in apoptosis [90]. Interestingly, it has been shown that T-AChE is translocated to the nucleus upon initiation of apoptosis [59], whilst a nuclear form of AChE has been identified in endothelial cells [69]. Given that the presence of AChE in the nucleus, particularly in non-neuronal cells, precludes its classical role in neurotransmission, it is reasonable to speculate that this molecule contributes in some capacity to the regulation of transcriptional events.…”

Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2

“…Meanwhile, other pathways like PI3K/Akt , protein kinase C (PKC) (Birikh et al, 2002), Nrf2 (Kosaka et al, 2009) may be involved in such signaling. Moreover, PC12 cells have been shown to synthesize nuclear and cytoplasmic isoforms of AChE (Santos et al, 2007). In fact this enzyme is expressed in several molecular forms, with different structural features but identical catalytic sites (Schweitzer, 1993).…”