1.Effects of benzo(a)pyrene on expressions of insulin-degrading enzyme and neprilysin in neuroglia cells.
Hui Feng ZHANG ; Huan Huan HUANG ; Yu Jia ZHAO ; Qing Ru LI ; Yu Ze QI ; Hui ZHOU
Journal of Peking University(Health Sciences) 2018;50(3):401-407
OBJECTIVE:
To investigate effects of benzo(a)pyrene (BaP) on expressions of insulin-degrading enzyme (IDE) and neprilysin (NEP) which have the ability to degrade β-amyloid (Aβ) in neuroglia cells.
METHODS:
Primary mix-neuroglia cells were cultured from newborn SD rats. After exposure to BaP, Aβ1-42 oligomer or Aβ1-42 fiber individually or jointly for 24 h, the cell survival rate was measured by cell counting kit-8 (CCK-8). Afterwards, the primary mix-neuroglia cells were divided randomly into six groups: Control group, BaP group (2.00 μmol/L), Aβ1-42 oligomer group (20.00 mg/L), BaP plus Aβ1-42 oligomer group, Aβ1-42 fiber group (20.00 mg/L) and BaP plus Aβ1-42 fiber group, of which BaP was pretreated for 12 h followed by cotreatment with different aggregated Aβ1-42. The expressions of IDE and NEP were measured by quantitative real-time polymerase chain reaction (qRT-PCR) for mRNA level and Western blotting for protein level.
RESULTS:
The cell survival rate showed no significant differences after treatment with BaP (≤20.00 μmol/L), Aβ1-42 oligomer (20.00, 40.00 mg/L), Aβ1-42 fiber (20.00, 40.00 mg/L) or cotreatment with BaP and Aβ1-42 oligomer or BaP and Aβ1-42 fiber. Compared with the control group, expressions of IDE and NEP in BaP-treated alone group had no obvious change; however, exposure to Aβ1-42 oligomer alone significantly increased the mRNA and protein level of IDE (P<0.05), and the BaP pretreatment could significantly inhibit the up-regulated expressions of IDE by Aβ1-42 oligomer (P<0.05); on the other hand, exposure either to Aβ1-42 fiber alone or under the BaP pretreatment did not change the mRNA and protein level of IDE and NEP obviously.
CONCLUSION
On the premise of no significant change of cell survival rate, BaP pretreatment inhibited the up-regulated expressions of IDE in primary mixed neuroglia cells under cotreatment with Aβ oligomer, indicating that BaP may disturb degradation of Aβ oligomer and cause deposition of β-amyloid and further induce cognitive decline and acceleration of Alzheimer.
Amyloid beta-Peptides
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Animals
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Benzo(a)pyrene
;
Blotting, Western
;
Insulysin/metabolism*
;
Neprilysin/metabolism*
;
Neuroglia/metabolism*
;
Rats
;
Rats, Sprague-Dawley
2.Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise.
Min Sun KIM ; Jun Seo GOO ; Ji Eun KIM ; So Hee NAM ; Sun Il CHOI ; Hye Ryun LEE ; In Sik HWANG ; Sun Bo SHIM ; Seung Wan JEE ; Su Hae LEE ; Chang Joon BAE ; Jung Sik CHO ; Jun Yong CHO ; Dae Youn HWANG
Laboratory Animal Research 2011;27(1):29-36
Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.
Animals
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Body Weight
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C-Peptide
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Diabetes Mellitus, Type 2
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Down-Regulation
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Glucose
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Glucose Transport Proteins, Facilitative
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Insulin
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Insulin Resistance
;
Insulysin
;
Rats
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Running
;
Swimming
3.Effect of rehabilitation training on insulin-resistance and hippocampus amyloid-beta peptide in rats with vascular dementia.
Hongwei WANG ; Qing YE ; Yan HUANG ; Huiying LIAO ; Haifen HUANG ; Yong YOU
Journal of Central South University(Medical Sciences) 2013;38(11):1167-1171
OBJECTIVE:
To investigate the effect of rehabilitation training on insulin-resistance and insulin degrading enzyme (IDE) in the hippocampus in rats with vascular dementia.
METHODS:
A total of 45 female Sprague-Dawley rats were randomly assigned into a rehabilitation group (n=15), an immobilization group (n=15), and a sham-operation group (n=15). The rats in the former 2 groups were operated on to establish the experimental vascular dementia model by bilateral common carotid artery permanent ligation. The rats' learning and memory were assessed 4 weeks after the operation. The plasma level of insulin was determined by ELISA at different time points after the operation. Immunohistochemical staining was used to detect the IDE expression in the hippocampus area.
RESULTS:
The rats in the rehabilitation group showed significantly better learning ability than that in the immobilization group (P<0.05). The plasma level of insulin in the rehabilitation group was lower than that in the immobilization group (P<0.05), IDE expression in the rehabilitation group was higher than that in the immobilization group (P<0.05) at 7 d and 28 d after the operation.
CONCLUSION
Rehabilitation can accelerate the recovery of learning and memory in rats with vascular dementia, and the mechanism is possibly related to the amelioration of insulin resistance and increase of IDE expression in the hippocampus.
Amyloid beta-Peptides
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analysis
;
Animals
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Dementia, Vascular
;
therapy
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Drugs, Chinese Herbal
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Female
;
Hippocampus
;
enzymology
;
Insulin
;
blood
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Insulin Resistance
;
Insulysin
;
analysis
;
Learning
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Memory
;
Rats
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Rats, Sprague-Dawley
4.Effect of tongluo xingnao effervescent tablet on learning and memory of AD rats and expression of insulin-degrading enzyme in hippocampus.
Yin-Jie ZHANG ; Yuan DAI ; Yong HU ; Yun-Tong MA ; Shi-Jun XU ; Yong-Yan WANG
China Journal of Chinese Materia Medica 2013;38(17):2863-2867
OBJECTIVETo study the effect of Tongluo Xingnao effervescent tablet on learning and memory of dementia rats induced by injection of Abeta25-35 in hippocampus and expression of insulin-degrading enzyme in hippocampus, in order to provide basis for preventing and treating senile dementia.
METHODThe dementia rat model was established by injecting Abeta25-35 in hippocampus. The rats were divided into the model control group, the Aricept (1.4 mg x kg(-1)) group, and Tongluo Xingnao effervescent tablet high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups. A sham operation group was established by injecting normal saline in hippocampus. The rats were orally given drugs for 90 days, once a day. Their learning and memory were tested by using Morris water maze. Immunohistochemistry and image analysis were utilized for a quantitative analysis on the expression of insulin-degrading enzyme in hippocampus.
RESULTTongluo Xingnao effervescent tablet could significantly shorten the escape latency of rats in the directional navigation test, prolong the retention time in the first quadrant dwell, decrease the retention time in the third quadrant dwell, increase the frequency of crossing the platform, show a more notable statistical significance than the model control group (P < 0.05). Additionally, it could also remarkably increase the average optical density of insulin-degrading enzyme in hippocampus, promote the expression of insulin-degrading enzyme in hippocampus, and show a more notable statistical significance than the model control group (P < 0.05).
CONCLUSIONTongluo Xingnao effervescent tablet has the effects of improving learning and memory capacity of AD rats and promoting the expression of insulin-degrading enzyme in hippocampus. Its effect in promoting intelligence will be related to increased insulin-degrading enzyme in hippocampus.
Alzheimer Disease ; drug therapy ; genetics ; metabolism ; psychology ; Animals ; Female ; Hippocampus ; drug effects ; metabolism ; Humans ; Insulysin ; genetics ; metabolism ; Learning ; drug effects ; Male ; Memory ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tablets ; administration & dosage
5.Maternal Lead Exposure Induces Down-regulation of Hippocampal Insulin-degrading Enzyme and Nerve Growth Factor Expression in Mouse Pups.
Xing LI ; Ning LI ; Hua Lei SUN ; Jun YIN ; Yu Chang TAO ; Zhen Xing MAO ; Zeng Li YU ; Wen Jie LI ; John D BOGDEN
Biomedical and Environmental Sciences 2017;30(3):215-219
Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life. This study was aimed to investigate the effects of lead exposure of pregnant mice on the expressions of insulin-degrading enzyme (IDE) and nerve growth factor (NGF) in the hippocampus of their offspring. Blood samples were collected from the tail vein, and after anesthetizing the pups, the brain was excised on postnatal day 21. Lead concentrations were determined by graphite furnace atomic absorption spectrophotometry, and the expressions of IDE and NGF were determined by immunohistochemistry and Western blotting. Results showed that the reduction in IDE and NGF expression in the hippocampus of pups might be associated with impairment of learning and memory and dementia induced by maternal lead exposure during pregnancy and lactation.
Animals
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Down-Regulation
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Female
;
Gene Expression Regulation, Developmental
;
drug effects
;
Gene Expression Regulation, Enzymologic
;
drug effects
;
Hippocampus
;
drug effects
;
growth & development
;
metabolism
;
Insulysin
;
genetics
;
metabolism
;
Lead
;
toxicity
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Mice
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Pregnancy
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Prenatal Exposure Delayed Effects
;
chemically induced
6.Effect of ginsenoside Rb1 on insulin signal transduction pathway in hippocampal neurons of high-glucose-fed rats.
Wen-Juan GU ; Di LIU ; Meng-Ren ZHANG ; Hong ZHANG
China Journal of Chinese Materia Medica 2014;39(6):1064-1068
OBJECTIVETo study the effect of ginsenoside Rb1 on GSKbeta/IDE signal transduction pathway and Abeta protein secretion in hippocampal neurons of high glucose-treated rats.
METHODHippocampal neurons of 24 h-old newly born SD rats were primarily cultured, inoculated in culture medium under different conditions, and then divided into the normal group, the high glucose group, the LiCl group and the Rb1 group. After being cultured for 72 h, the expressions of their phosphorylated GSK3beta, total GSK3beta and IDE protein were detected by Western blotting analysis. The mRNA expressions of GSK3beta and IDE were determined by RT-PCR. The ELISA assay was used to detect the secretion of Abeta protein in cell supernatant.
RESULTCompared with the normal group, the high glucose group showed increase in the p/tGSK3beta protein ratio and the secretion of Abeta protein and decrease in IDE protein and mRNA (P < 0.05). Compared with the high glucose group, both Rb1 and LiCl groups showed decrease in the p/tGSK3beta protein ratio and the expression of Abeta protein and increase in IDE protein and mRNA expression (P < 0.05). Compared with the LiCl group, the Rb1 group showed no significant difference in the expressions of p/tGSK3beta protein, IDE protein, mRNA and Abeta protein expression. In addition, the GSK3beta mRNA expression of the four groups had no significant difference.
CONCLUSIONGinsenoside Rb1 may reduce the secretion of Abeta protein in hippocampal neurons by reducing the phosphorylation of GSK3beta, down-regulating the ratio of pGSK3beta/GSK3beta and upregulating the expression of IDE.
Amyloid beta-Peptides ; genetics ; metabolism ; secretion ; Animals ; Dietary Carbohydrates ; adverse effects ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Glucose ; adverse effects ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Hippocampus ; cytology ; Insulin ; metabolism ; Insulysin ; genetics ; metabolism ; Neurons ; cytology ; drug effects ; metabolism ; secretion ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects