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Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice.

Durrant AR, Tamayev L, Anglister L - Front Mol Neurosci (2012)

Bottom Line: The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood.However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited.While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada, IMRIC, Faculty of Medicine, Hebrew University Medical School Jerusalem, Israel.

ABSTRACT
The cholinesterases, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) (pseudocholinesterase), are abundant in the nervous system and in other tissues. The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates AChE and BChE in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy (DMD) and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T) is a negative modulator of BChE, but not of AChE, in male mouse sera. T-removal elevated both BChE activity and the BChE/AChE ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

No MeSH data available.


Related in: MedlinePlus

Effect of orchidectomy and T-replacement appears to be on BChE, not on AChE. Activities in wt sera of BChE (A,B) and AChE (C) were determined colorimetrically (A) or radiometrically (B,C) with appropriate substrates and selective inhibitors as described in the legend to Figure 2. Values are the mean ± SEM for 6–8 samples per group (sham group, n = 3). BChE levels in gonadectomized animals (dashed line in A) differ significantly from those in intact, T-treated and sham animals: Data were analyzed by One-Way ANOVA, showing statistical significance in A (p « 0.0002) and in B (p « 0.0001), with Tukey's post-hoc revealing significant differences (*) between castrated male (cas, shaded column) and the other three groups: intact male (male) (p < 0.0003), castrated with T-replacement (cas + T) (p < 0.0002) or sham (p < 0.0002). All other comparisons showed insignificance (p > 0.05): male compared to cas + T (p = 0.086), or to sham (p = 0.07), and cas + T compared to sham (p = 0.92). Similarly, post-hoc test in B showed significant difference between cas and the other groups: male (p < 0.001), cas + T (p < 0.0004), and sham (p < 0.001), which were very similar. No significant changes were observed in AChE activity (C).
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Figure 3: Effect of orchidectomy and T-replacement appears to be on BChE, not on AChE. Activities in wt sera of BChE (A,B) and AChE (C) were determined colorimetrically (A) or radiometrically (B,C) with appropriate substrates and selective inhibitors as described in the legend to Figure 2. Values are the mean ± SEM for 6–8 samples per group (sham group, n = 3). BChE levels in gonadectomized animals (dashed line in A) differ significantly from those in intact, T-treated and sham animals: Data were analyzed by One-Way ANOVA, showing statistical significance in A (p « 0.0002) and in B (p « 0.0001), with Tukey's post-hoc revealing significant differences (*) between castrated male (cas, shaded column) and the other three groups: intact male (male) (p < 0.0003), castrated with T-replacement (cas + T) (p < 0.0002) or sham (p < 0.0002). All other comparisons showed insignificance (p > 0.05): male compared to cas + T (p = 0.086), or to sham (p = 0.07), and cas + T compared to sham (p = 0.92). Similarly, post-hoc test in B showed significant difference between cas and the other groups: male (p < 0.001), cas + T (p < 0.0004), and sham (p < 0.001), which were very similar. No significant changes were observed in AChE activity (C).

Mentions: Sera from orchidectomized 21 week adult male wt mice were analyzed for ChE activities (Figure 3). Gonadectomy raised BChE activities in adult male mice serum by 20–37% (p < 0.001), whether measured on BTCh, or on ACh in the presence of a selective AChE inhibitor (Figure 3A and B, respectively)


Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice.

Durrant AR, Tamayev L, Anglister L - Front Mol Neurosci (2012)

Effect of orchidectomy and T-replacement appears to be on BChE, not on AChE. Activities in wt sera of BChE (A,B) and AChE (C) were determined colorimetrically (A) or radiometrically (B,C) with appropriate substrates and selective inhibitors as described in the legend to Figure 2. Values are the mean ± SEM for 6–8 samples per group (sham group, n = 3). BChE levels in gonadectomized animals (dashed line in A) differ significantly from those in intact, T-treated and sham animals: Data were analyzed by One-Way ANOVA, showing statistical significance in A (p « 0.0002) and in B (p « 0.0001), with Tukey's post-hoc revealing significant differences (*) between castrated male (cas, shaded column) and the other three groups: intact male (male) (p < 0.0003), castrated with T-replacement (cas + T) (p < 0.0002) or sham (p < 0.0002). All other comparisons showed insignificance (p > 0.05): male compared to cas + T (p = 0.086), or to sham (p = 0.07), and cas + T compared to sham (p = 0.92). Similarly, post-hoc test in B showed significant difference between cas and the other groups: male (p < 0.001), cas + T (p < 0.0004), and sham (p < 0.001), which were very similar. No significant changes were observed in AChE activity (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378013&req=5

Figure 3: Effect of orchidectomy and T-replacement appears to be on BChE, not on AChE. Activities in wt sera of BChE (A,B) and AChE (C) were determined colorimetrically (A) or radiometrically (B,C) with appropriate substrates and selective inhibitors as described in the legend to Figure 2. Values are the mean ± SEM for 6–8 samples per group (sham group, n = 3). BChE levels in gonadectomized animals (dashed line in A) differ significantly from those in intact, T-treated and sham animals: Data were analyzed by One-Way ANOVA, showing statistical significance in A (p « 0.0002) and in B (p « 0.0001), with Tukey's post-hoc revealing significant differences (*) between castrated male (cas, shaded column) and the other three groups: intact male (male) (p < 0.0003), castrated with T-replacement (cas + T) (p < 0.0002) or sham (p < 0.0002). All other comparisons showed insignificance (p > 0.05): male compared to cas + T (p = 0.086), or to sham (p = 0.07), and cas + T compared to sham (p = 0.92). Similarly, post-hoc test in B showed significant difference between cas and the other groups: male (p < 0.001), cas + T (p < 0.0004), and sham (p < 0.001), which were very similar. No significant changes were observed in AChE activity (C).
Mentions: Sera from orchidectomized 21 week adult male wt mice were analyzed for ChE activities (Figure 3). Gonadectomy raised BChE activities in adult male mice serum by 20–37% (p < 0.001), whether measured on BTCh, or on ACh in the presence of a selective AChE inhibitor (Figure 3A and B, respectively)

Bottom Line: The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood.However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited.While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada, IMRIC, Faculty of Medicine, Hebrew University Medical School Jerusalem, Israel.

ABSTRACT
The cholinesterases, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) (pseudocholinesterase), are abundant in the nervous system and in other tissues. The role of AChE in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s) of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates AChE and BChE in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy (DMD) and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While AChE in mdx-sera is elevated, BChE is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T) is a negative modulator of BChE, but not of AChE, in male mouse sera. T-removal elevated both BChE activity and the BChE/AChE ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

No MeSH data available.


Related in: MedlinePlus