Objective To investigate the relationships of nuclear factor кB (NF-кB) activation with protein kinase B (Akt) and glycogen synthase kinase 3β (GSK-3β) during amyloid-β (Aβ) (25-35) -induced apoptosis in pheochromocytoma cells (PC12 cells) of rats. Methods Apoptosis in PC12 cells was induced by A(25-35). The activities of Akt, GSK-3β and NF-кB were analyzed in this process. The Akt and GSK-3β pathways were blocked by their specific inhibitors, respectively, and the relationships of Akt and, GSK-3β with NF-кB during Aβ(25-35)-induced apoptosis in PC12 cells were determined. Results Aβ(25-35) induced apoptosis was in a dose-dependent manner. With 0, 5, 10, 20 μmol/L and 40 μmol/L Aβ(25-35) treaing for 48 h, the apoptosis rates of PC12 cells were (3. 01 ± 0.03)%, (3.08 ±0.03)%, (25.32 ± 0.76)%, ( 42.88 ± 0.60 )% and ( 60.85 ± 2.39 )% , respectively. Compared to control, both Akt and GSK-3β were suppressed during apoptosis, at meantime NF-кB was activated. The inhibited Akt activity by wortmannin leaded to decreased NF-кB activatity and increased GSK-3β activatity. Suppression of GSK-3β with its specific inhibitor LiCl caused the decreased activation of NF-кB too, but it had no significant influence on Akt activity. Conclusions These results suggest that both Akt and GSK-3β are upstream regulators of NF-кB. They co-regulate the activation of NF-кB during Aβ(25-35)-induced apoptosis in PC12 cells. This study contributes to the theoretical base for the pathogenesis of Alzheimer disease (AD) , and provides a new idea to AD prevention and therapy.

Animals ; Disease Models, Animal ; Hematology ; Mice ; Mice, Transgenic

OBJECTIVE: Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population. METHODS: A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke. RESULTS: All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups. CONCLUSION In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.
Humans ; Cholesterol, LDL ; Retrospective Studies ; Percutaneous Coronary Intervention/adverse effects* ; Coronary Artery Disease/surgery* ; Cholesterol ; Cholesterol, HDL ; Stroke/etiology* ; Treatment Outcome ; Risk Factors