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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

T-regulation of BChE activity in male mdx sera. BChE activities were measured colorimetrically with BTCh as substrate in sera of intact, castrated, castrated with T-replacement, and sham operated wt and mdx □ mice, (as in Figure 3A). Values, mean ± SEM for samples taken from 4 to 8 mice per group (sham group, n = 3). *p < 0.001 between BChE levels in castrated wt and in intact, T-treated, and sham mice sera (of either wt or mdx strains). **p < 0.05 (detailed in 3) between BChE levels in castrated mdx and in intact, T-treated, and sham mdx mice sera. #Significant difference between BChE level in mdx and wt in all the experimental groups (p-values are listed in 2). The dashed black and red lines indicate BChE levels in agonadal and gonadal wt sera, respectively.
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Figure 4: T-regulation of BChE activity in male mdx sera. BChE activities were measured colorimetrically with BTCh as substrate in sera of intact, castrated, castrated with T-replacement, and sham operated wt and mdx □ mice, (as in Figure 3A). Values, mean ± SEM for samples taken from 4 to 8 mice per group (sham group, n = 3). *p < 0.001 between BChE levels in castrated wt and in intact, T-treated, and sham mice sera (of either wt or mdx strains). **p < 0.05 (detailed in 3) between BChE levels in castrated mdx and in intact, T-treated, and sham mdx mice sera. #Significant difference between BChE level in mdx and wt in all the experimental groups (p-values are listed in 2). The dashed black and red lines indicate BChE levels in agonadal and gonadal wt sera, respectively.

Mentions: We went on to examine whether orchidectomy raises BChE levels also in the sera of mdx mice, and whether, as a consequence, the high agonadal baseline ChE levels seen in wt mice sera can be reached. The data presented in Table 2 and Figure 4 reveal low levels of BChE in the sera of control adult mdx males (32.2–48.6 assay units). Although levels increase substantially after gonadectomy (48.7–61.9 assay units), by an average of 35%, the BChE deficiency observed in untreated mdx mice is sustained (Figure 4): thus, the agonadal “baseline” level in mdx mice was significantly below the baseline level in wt agonadal mice (29%, p < 0.002). It was slightly lower than the level in control wt mice (14%, p = 0.06) or in sham-operated wt mice. As in wt mice, T-replacement reversed the effect of orchidectomy on BChE activity. Thus, after orchidectomy, the BChE in mdx circulation may almost reach the gonadal baseline level of BChE activity in the serum of intact male wt mice, but not the agonadal baseline level in the serum of castrated wt mice.


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

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

T-regulation of BChE activity in male mdx sera. BChE activities were measured colorimetrically with BTCh as substrate in sera of intact, castrated, castrated with T-replacement, and sham operated wt and mdx □ mice, (as in Figure 3A). Values, mean ± SEM for samples taken from 4 to 8 mice per group (sham group, n = 3). *p < 0.001 between BChE levels in castrated wt and in intact, T-treated, and sham mice sera (of either wt or mdx strains). **p < 0.05 (detailed in 3) between BChE levels in castrated mdx and in intact, T-treated, and sham mdx mice sera. #Significant difference between BChE level in mdx and wt in all the experimental groups (p-values are listed in 2). The dashed black and red lines indicate BChE levels in agonadal and gonadal wt sera, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: T-regulation of BChE activity in male mdx sera. BChE activities were measured colorimetrically with BTCh as substrate in sera of intact, castrated, castrated with T-replacement, and sham operated wt and mdx □ mice, (as in Figure 3A). Values, mean ± SEM for samples taken from 4 to 8 mice per group (sham group, n = 3). *p < 0.001 between BChE levels in castrated wt and in intact, T-treated, and sham mice sera (of either wt or mdx strains). **p < 0.05 (detailed in 3) between BChE levels in castrated mdx and in intact, T-treated, and sham mdx mice sera. #Significant difference between BChE level in mdx and wt in all the experimental groups (p-values are listed in 2). The dashed black and red lines indicate BChE levels in agonadal and gonadal wt sera, respectively.
Mentions: We went on to examine whether orchidectomy raises BChE levels also in the sera of mdx mice, and whether, as a consequence, the high agonadal baseline ChE levels seen in wt mice sera can be reached. The data presented in Table 2 and Figure 4 reveal low levels of BChE in the sera of control adult mdx males (32.2–48.6 assay units). Although levels increase substantially after gonadectomy (48.7–61.9 assay units), by an average of 35%, the BChE deficiency observed in untreated mdx mice is sustained (Figure 4): thus, the agonadal “baseline” level in mdx mice was significantly below the baseline level in wt agonadal mice (29%, p < 0.002). It was slightly lower than the level in control wt mice (14%, p = 0.06) or in sham-operated wt mice. As in wt mice, T-replacement reversed the effect of orchidectomy on BChE activity. Thus, after orchidectomy, the BChE in mdx circulation may almost reach the gonadal baseline level of BChE activity in the serum of intact male wt mice, but not the agonadal baseline level in the serum of castrated wt mice.

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