Expression of high affinity choline transporter during mouse development in vivo and its upregulation by NGF and BMP-4 in vitro

Berse, Brygida; Szczecińska, Weronika; López-Coviella, Ignacio; Madziar, Beata; Zemelko, V. I.; Kaminski, Rafal; Kozar, Katarzyna; Lips, Katrin Susanne; Pfeil, Uwe; Blusztajn, Jan Krzysztof

doi:10.1016/j.devbrainres.2005.03.013

Cited by 28 publications

(37 citation statements)

References 52 publications

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“…The reduction of ChAT-induced CHT1 transcription was significantly correlated with the concentration of LY294002 used for the treatment. A previous report showed that LY294002 treatment reduces endogenous CHT1 expression in mouse primary septal culture as well as NGF-induced CHT1 expression (34). Our observation of reduction in CHT expression by LY294002 appears to be consistent with the LY294002 effect on endogenous CHT1 expression.…”

Section: Discussionsupporting

confidence: 79%

“…Synergic up-regulation of CHT1 and ChAT is also observed when superior cervical ganglia are treated with leukemia inhibitory factor (41). It has been shown that simultaneous up-regulation of CHT1 and VACHT is induced when primary septal cells are stimulated with NGF (34). The effects of NGF on cholinergic gene expression are known to be dependent on PI3K signaling (42), and treatment with an inhibitor of PI3K inhibits the effect of NGF on CHT1 expression (34).…”

Section: Discussionmentioning

confidence: 99%

“…ChAT-A previous study showed that CHT1 expression is induced in primary septal cells by stimulation with nerve growth factor (NGF) (34). It has also been reported that treatment with an inhibitor of phosphatidylinositol 3-kinase (PI3K) prevents this effect of NGF on CHT1 expression (34).…”

Section: Inhibition Of Pi3k Reduced the Up-regulation Of Cht1 Bymentioning

confidence: 99%

“…It has also been reported that treatment with an inhibitor of phosphatidylinositol 3-kinase (PI3K) prevents this effect of NGF on CHT1 expression (34). To determine whether PI3K inhibition could reverse CHT1 induction by ChAT, we treated wt-hChAT-GFP cells with 10 M LY294002 in DMSO for 72 h. Although LY294002 treatment reduced the cell number of both wt-hChAT-GFP and GFP alone cell cultures, the mRNA expression level of CHAT mRNA in the surviving cells was not significantly different to that in cells treated with the same amount of control DMSO (Fig.…”

Section: Inhibition Of Pi3k Reduced the Up-regulation Of Cht1 Bymentioning

confidence: 99%

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Nuclear Choline Acetyltransferase Activates Transcription of a High-affinity Choline Transporter

Matsuo

Bellier

Nakagawa

et al. 2011

Journal of Biological Chemistry

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Choline acetyltransferase (ChAT) synthesizes the neurotransmitter, acetylcholine, at cholinergic nerve terminals. ChAT contains nuclear localization signals and is also localized in the nuclei of neural and non-neuronal cells. Nuclear ChAT might have an as yet unidentified function, such as transcriptional regulation. In this study, we investigated the alteration of candidate gene transcription by ChAT. We chose high affinity choline transporter (CHT1) and vesicular acetylcholine transporter (VACHT) as candidate genes, which function together with ChAT in acetylcholine production. Using SH-SY5Y human neuroblastoma cells stably expressing wild-type human ChAT, we found that overexpressed ChAT enhanced transcription of the CHT1 gene but not the VACHT gene. In contrast, nuclear localization signal disrupted, and catalytically inactive mutant ChATs could not induce, CHT1 expression. Additionally, ChAT did not alter CHT1 expression in non-neuronal HEK293 cells. Our results suggest that ChAT activates the transcription of selected target genes in neuronal cells. Both enzymatic activity and nuclear translocation of ChAT are required for its transcriptional enhancement.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of Pi3k Reduced the Up-regulation Of Cht1 Bymentioning

confidence: 99%

Section: Inhibition Of Pi3k Reduced the Up-regulation Of Cht1 Bymentioning

confidence: 99%

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Nuclear Choline Acetyltransferase Activates Transcription of a High-affinity Choline Transporter

Matsuo

Bellier

Nakagawa

et al. 2011

Journal of Biological Chemistry

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“…The majority of the data available to date from several mammalian species has revealed coordinated expression of CHT and the other two cholinergic genes, ChAT and VAChT, contained within the cholinergic locus (Apparsundaram et al, 2001;Apparsundaram et al, 2000;Berse et al, 2005;Oda et al, 2004;Okuda et al, 2000). The results presented here demonstrate that, in spinal cord-derived NSC-19 cells, cAMP-evoked signaling pathways differentially regulate CHT and the cholinergic locus.…”

Section: Discussionmentioning

confidence: 52%

Differential regulation of the high affinity choline transporter and the cholinergic locus by cAMP signaling pathways

Brock¹,

Nickel²,

Madziar³

et al. 2007

Brain Research

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Synthesis, storage and release of acetylcholine (ACh) require the expression of several specialized enzymes, including choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and the high-affinity choline transporter (CHT). Extracellular factors that regulate CHT expression and their signaling pathways remain poorly characterized. Using the NSC-19 cholinergic cell line, derived from embryonic spinal cord, we compared the effects of the second messenger cAMP on the expression of CHT and the cholinergic locus containing the ChAT and VAChT genes. Treatment of NSC-19 cells with dbcAMP and forskolin, thus increasing intracellular cAMP levels, significantly reduced CHT mRNA expression, while it upregulated ChAT/VAChT mRNA levels and ChAT activity. The cAMP-induced CHT downregulation was independent of PKA activity, as shown in treatments with the PKA inhibitor H-89. The alternative Epac-Rap pathway, when stimulated by a specific Epac activator, led to significant downregulation of CHT and ChAT, and, to a lesser extent, VAChT. In contrast, the PKA activator 6-BNZ-cAMP stimulated the expression of all three genes, but with varying concentration-dependence profiles. Our results indicate that elevations of intraneuronal cAMP concentration have differential effects on the cholinergic phenotype, depending on the involvement of different downstream effectors. Interestingly, although CHT is expressed predominantly in cholinergic cells, its regulation appears to be distinct from that of the cholinergic locus.

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Sex‐specific declines in cholinergic‐targeting tRNA fragments in the nucleus accumbens in Alzheimer's disease

Shulman

Dubnov

Zorbaz

et al. 2023

Alzheimer's & Dementia

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IntroductionFemales with Alzheimer's disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors to both these phenomena, we pursued changes in transfer RNS (tRNA) fragments (tRFs) targeting cholinergic transcripts (CholinotRFs).MethodsWe analyzed small RNA‐sequencing (RNA‐Seq) data from the nucleus accumbens (NAc) brain region which is enriched in cholinergic neurons, compared to hypothalamic or cortical tissues from AD brains; and explored small RNA expression in neuronal cell lines undergoing cholinergic differentiation.ResultsNAc CholinotRFs of mitochondrial genome origin showed reduced levels that correlated with elevations in their predicted cholinergic‐associated mRNA targets. Single‐cell RNA seq from AD temporal cortices showed altered sex‐specific levels of cholinergic transcripts in diverse cell types; inversely, human‐originated neuroblastoma cells under cholinergic differentiation presented sex‐specific CholinotRF elevations.DiscussionOur findings support CholinotRFs contributions to cholinergic regulation, predicting their involvement in AD sex‐specific cholinergic loss and dementia.

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Expression of high affinity choline transporter during mouse development in vivo and its upregulation by NGF and BMP-4 in vitro

Cited by 28 publications

References 52 publications

Nuclear Choline Acetyltransferase Activates Transcription of a High-affinity Choline Transporter

Nuclear Choline Acetyltransferase Activates Transcription of a High-affinity Choline Transporter

Differential regulation of the high affinity choline transporter and the cholinergic locus by cAMP signaling pathways

Sex‐specific declines in cholinergic‐targeting tRNA fragments in the nucleus accumbens in Alzheimer's disease

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