1.Effects of phosphatidylinositol-3 kinase/serine threonine kinase pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 in the hippocampus neurons
Jieying LI ; Yong YAN ; Zhiyou CAI ; Zhanhui FENG ; Hua ZHANG ; Fang WU ; Tao MENG ; Zhengwei DAI
Chinese Journal of Neurology 2009;42(11):737-741
Objective To investigate the effect of phosphatidylinesitol-3 kinase/serine threonine kinase (PI3K/Akt) signaling pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in the hippocampus neurons of rat brain. Methods Forty SD rats were randomly divided into 4 groups: blank control group, sham-operated group, insulin group and wortmannin group. Insulin or the specific inhibitor of PI3K, wortmannin was injected into hippocampus neurons to activate or inhibit the signaling pathway in insulin group or wortmannin group, respectively. Immunoprecipitation and Western blot were used to analyze the proteins levels of PI3K/Akt and BACE1. Results In insulin treatment group,among the proteins downstream of signaling pathway, expression of Akt increased (0. 952±0.060 vs 0.835±0.029,t=4.9150, P=0.0001), phospho-Akt set473 increased (0.800±0.075 vs 0.657± 0.025,t=4.5598, P=0.0002), phospho-GSK-3α decreased (0.604±0.062 vs 0.726±0.041, t= 3.5871, P=0.0018 ), and the expression of mature BACE1 and β-CTF significantly decreased. In wortmannin group, the expression of Akt and phospho-Akt ser473 were inhibited; phospho-GSK-3α increased ; mature BACEI (1.004±0.096) and β-CTF (1.031±0.048) increased (t=11.5980, P= 0.0000 and t =4.2194, P =0.0004, respectively). Conclusions PI3K/Akt signaling pathway might effect the expression of BACE1, in which impaired signaling pathway may cause the amyloid precursor protein to be easily processed by BACE1, and thus involves the pathology of Alzheimer' s disease.
2.A preliminary clinical application of sICAM-1 RIA in three kinds of thyroid disease.
Mei LU ; Peihua FANG ; Zhiyou ZHANG ; Hongpeng HE ; Shuo GAO ; Bingzhang HOU ; Rongxiu ZHENG ; Qian XIAO ; Liping YANG
Chinese Medical Journal 2002;115(10):1552-1555
OBJECTIVETo examine serum levels of sICAM-1 from normal controls and patients with thyroid diseases (simple goitre, Graves' disease or Hashimoto's thyroiditis) with (125)I-sICAM-1 RIA established in our lab.
METHODSUsing (125)I-sICAM-1 RIA, serum sICAM-1 levels of 400 healthy individuals as the normal group and 1020 patients with simple goitre (SG), Graves' disease (GD) or Hashimoto's thyroiditis (HT) were examined for a comporative chinical study.
RESULTSThe serum level of sICAM-1 (x +/- s) in the normal group was 168.43 +/- 36.23 micro g/L. There was no significant difference between the normal and SG groups (P > 0.05), whereas the serum levels of sICAM-1 in autoimmune thyroid diseases (GD or HT) were higher than those in the normal or SG groups (P < 0.05, respectively). After GD patients received one of three medical treatments, their serum sICAM-1 levels decreased (P < 0.05). After GD patients were treated and their thyroid function decreased to normal, their serum sICAM-1 levels were lower than those in relapsed GD patients (P < 0.05).
CONCLUSIONSsICAM-1 RIA can be used to examine autoimmune thyroid diseases. Serum levels of sICAM-1 can be used as a parameter in diagnosing autoimmune thyroid disease and in evaluating the effects of therapy, drug administration or relapse in GD.
Adult ; Aged ; Female ; Goiter ; blood ; diagnosis ; Graves Disease ; blood ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Middle Aged ; Radioimmunoassay ; Thyroiditis, Autoimmune ; blood ; diagnosis
3.Supervillin regulates convergence and extension movements via Wnt/β⁃catenin pathway in zebrafish embryos
Lizhu Hu ; Chenggang Zhao ; Junqi Fan ; Haoran Yang ; Shangrong Zhang ; Xueran Chen ; Zhiyou Fang
Acta Universitatis Medicinalis Anhui 2022;57(2):218-223
Objective :
To explore the role and molecular mechanism of Supervillin in zebrafish embryo development.
Methods :
Clustal Omega and DNAman software were used to analyze and compare the homology of amino acid sequences of Svil and SVIL in zebrafish and human. The expression pattern of Svila (subtype of Svil protein in zebrafish) during early embryonic development was analyzed by RT⁃PCR and in situ hybridization. Svila expression in zebrafish was inhibited by injecting morphinos ( MO) , and morphological changes of embryos were observed. The expression and nuclear localization of β ⁃catenin protein were detected by Western blot , and the expression of Wnt/β⁃catenin target gene was detected by RT⁃PCR.
Results :
During the early embryonic development of zebrafish , Svila was maternally expressed and showed an upward trend with the development process. The expression of Svila was reduced by MO , and the development of zebrafish embryos was distorted and the body axis was bent , which might be related to the blocked movement of concentrated extension of embryos. Further studies showed that Svila expression affected β⁃catenin nuclear transport and Wnt/β⁃catenin signaling pathway activation.
Conclusion
Svila regulates the concentrated extension movement of zebrafish embryos by activating the Wnt/β⁃catenin signaling pathway.