Control levels of acetylcholinesterase expression in the mammalian skeletal muscle

Grubič, Zoran; Zajc-Kreft, Katarina; Brank, Martina; Marš, Tomaž; Komel, Rado; Miranda, Armand F.

doi:10.1016/s0009-2797(99)00041-1

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…For example, the dramatic decrease in muscle AChE mRNA levels observed after denervation was attributed to diminished transcript stability as determined by in vitro mRNA stability assays (Grubic et al, 1999;Boudreau-Lariviere et al, 2000). To date, however, the elements and factors mediating this effect have yet to be identified.…”

Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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After axotomy, expression of acetylcholinesterase (AChE) is greatly reduced in the superior cervical ganglion (SCG); however, the molecular events involved in this response remain unknown. Here, we first examined AChE mRNA levels in the brain of transgenic mice that overexpress human HuD. Both in situ hybridization and reverse transcription-PCR demonstrated that AChE transcript levels were increased by more than twofold in the hippocampus of HuD transgenic mice. Additionally, direct interaction between the HuD transgene product and AChE mRNA was observed. Next, we examined the role of HuD in regulating AChE expression in intact and axotomized rat SCG neurons. After axotomy of the adult rat SCG neurons, AChE transcript levels decreased by 50 and 85% by the first and fourth day, respectively. In vitro mRNA decay assays indicated that the decrease in AChE mRNA levels resulted from changes in the stability of presynthesized transcripts. A combination of approaches performed using the region that directly encompasses an adenylate and uridylate (AU)-rich element within the AChE 3Ј-untranslated region demonstrated a decrease in RNA-protein complexes in response to axotomy of the SCG and, specifically, a decrease in HuD binding. After axotomy, HuD transcript and protein levels also decreased. Using a herpes simplex virus construct containing the human HuD sequence to infect SCG neurons in vivo, we found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy. Together, the results of this study demonstrate that AChE expression in neurons of the rat SCG is regulated via post-transcriptional mechanisms that involve the AU-rich element and HuD.

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Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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show abstract

“…Denervation probably results in very low sarcoplasmic Ca 2ϩ levels and inactive calcineurin. Seemingly, if the number of activations decreases under some threshold, then a positive regulatory mechanism, which allows for the highest AChE mRNA levels in rarely activated fast muscle fibers, is overwhelmed by increased rate of AChE mRNA degradation, typical for denervation (Grubič et al, 1999;Boudreau-Lariviere et al, 2000b), which is induced by some calcineurin-independent mechanism.…”

Section: Calcineurin Signaling Pathway and Muscle Ache Regulationmentioning

confidence: 99%

The Role of Muscle Activation Pattern and Calcineurin in Acetylcholinesterase Regulation in Rat Skeletal Muscles

Pregelj¹,

Trinkaus²,

Zupan³

et al. 2007

J. Neurosci.

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Acetylcholinesterase (AChE) expression in fast rat muscles is approximately fourfold higher than in slow muscles. We examined whether different muscle activation patterns are responsible for this difference and whether the calcineurin signaling pathway is involved in AChE regulation. The slow soleus and fast extensor digitorum longus (EDL) muscles were directly or indirectly stimulated by a tonic lowfrequency or a phasic high-frequency pattern of electric impulses. The phasic, but not tonic, stimulation increased the AChE mRNA levels in denervated soleus muscles to those in the normal EDL and maintained high levels of AChE mRNA in denervated EDL muscles. Therefore, muscle activation pattern is the predominant regulator of extrajunctional AChE expression in rat muscles. Indirect phasic stimulation of innervated muscles, imposed on their natural pattern of neural activation, did not increase the AChE transcript levels in the soleus, whereas a 30% reduction was observed in the EDL muscles. A low number of impulses per day is therefore prerequisite for high AChE expression. Treatment by tacrolimus and cyclosporin A, two inhibitors of calcineurin (but not by a related substance rapamycin, which does not inhibit calcineurin), increased the levels of AChE transcripts in the control soleus muscles and in tonically electrically stimulated soleus and EDL muscles, even to reach those in the control EDL muscles. Therefore, tonic muscle activation reduces the extrajunctional levels of AChE transcripts by activating the calcineurin signaling pathway. In denervated soleus and EDL muscles, tacrolimus did not prevent the reduction of AChE mRNA levels, indicating that a calcineurin-independent suppressive mechanism was involved.

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Control levels of acetylcholinesterase expression in the mammalian skeletal muscle

Cited by 2 publications

References 27 publications

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

The Role of Muscle Activation Pattern and Calcineurin in Acetylcholinesterase Regulation in Rat Skeletal Muscles

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