EFFECTS OF INSULIN-LIKE GROWTH FACTOR 1 ON β-AMYLOID INDUCED NEURON APOPTOSIS AND TAU PHOSPHORYLATION
- VernacularTitle:胰岛素样生长因子1对β样淀粉蛋白引起的神经元凋亡和tau 蛋白磷酸化的作用
- Author:
Changhong XING
;
Ying PENG
;
Zuoping XIE
- Publication Type:Journal Article
- Keywords:
insulin-like growth factor 1;
β-amyloid;
apoptosis;
tau;
flow cytometry;
Alzheimer's disease
- From:
Chinese Journal of Neuroanatomy
2005;21(6):569-575
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to elucidate the protective and anti-apoptotic effects of insulin-like growth factor 1 ( IGF-1 ) against β-amyloid (Aβ) and investigate the effect of IGF-1 on Aβ-induced tau phosphorylation. Cell viability was measured using the MTT (3-(4,5-dimethylthiazolyl-2 )-2,5-diphenyltetrazolium bromide) assay, early apoptosis and late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide (PI) double staining, and morphology was examined by Hoechst 33342 staining. Tau phosphorylation was detected using AT8 immunostaining. Preincubation of cultured rat hippocampal neurons with IGF-1 for 24 h prevented cytotoxicity induced by Aβ25-35 for 48 h. The MTT value significantly increased from 54.51% to 61.8% of the control group, and the percentage of Hoechst 33342-positive cells decreased from 30.77% to 22.81%. Incubation with Aβ25-35 for 48 h caused a marked increase in the percentages of Annexin V-FITC single-labeled cells (Annexin V +/PI-) and Annexin V/PI double-stained cells (Annexin V +/PI + ) (3.41% and 19.47% , respectively), which were significantly decreased by pretreatment with 100 ng/ml of IGF-1 for 24 h (to 2.98% and 15.16% , respectively). Aβ25-35 treatment increased tau phosphorylation and AT8 positive cells were 41.84%. This effect could be inhibited by different concentrations of IGF-1. Our findings showed that IGF-1 protected against Aβ-induced cytotoxicity, decreased the percentage of early and late apoptosis/necrosis cells, and inhibited tau phosphorylation, which may be the cellular mechanisms for its neuroprotective action.
