ABSTRACT
Amyloid ß-protein (Aß) is believed to contribute to the development of Alzheimer's disease (AD). Here we showed that Aß25-35 rapidly caused activation of autophagy, subsequently leading to reduction of autophagy associated with cellular apoptosis. Further investigation revealed that the accumulation of ß-arrestin 1 (ARRB1) caused by Aß25-35 contributed to the induction of autophagic flux. The depletion of ARRB1 led to decreases in the expression of LC3B, Atg7, and Beclin-1, which are essential for the initiation of autophagy. ARRB1 depletion also reduced downstream ERK activity and promoted Aß25-35-induced cell death. As with ARRB1, transient upregulation of ARRB2 by Aß25-35 was observed after short treatment durations, whereas genetic reduction of ARRB2 caused a marked increase in the expression of the α7nAch receptor at the cell surface, which resulted in partial reversal of Aß25-35-induced cell death. Although expression of both ARRB1 and ARRB2 was reduced in serum from patients with AD, the levels of ARRB1 were much lower than those of ARRB2 in AD. Thus, our findings indicate that ARRB1/2 play different roles in Aß25-35 cytotoxicity, which may provide additional support for exploring the underlying molecular mechanism of AD.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/toxicity , Autophagy , Peptide Fragments/toxicity , beta-Arrestin 1/metabolism , beta-Arrestin 2/metabolism , Cell Death , Cell Line, Tumor , Humans , Neurons/drug effects , Neurons/metabolism , alpha7 Nicotinic Acetylcholine Receptor/genetics , alpha7 Nicotinic Acetylcholine Receptor/metabolism , beta-Arrestin 1/genetics , beta-Arrestin 2/geneticsABSTRACT
BACKGROUND: Leukemia is the most common pediatric malignancy. Many children with leukemia display behavioral and emotional problems. Promoting children's psychological development and quality of life during hospitalization is an important activity carried out by health professionals. OBJECTIVE: The objective of this study was to describe the experiences and feelings of Chinese children with leukemia in the hospital. METHOD: In-depth interviews were conducted with Chinese children with leukemia using a descriptive qualitative research method. The data were analyzed using content analysis. RESULTS: Twenty-nine children with leukemia were interviewed. Almost all children had negative experiences and feelings during the early stage of hospitalization, and there were 3 levels of adaptation that they displayed: inability to adapt to hospitalization, a sense of being compelled to accept hospitalization, and adaptation to hospitalization. CONCLUSIONS: Three factors are associated with children's psychological distress, including the duration of treatment, children's personality, and age. Children of a younger age, with more extrovert personalities and who were undergoing longer treatment courses, adapted to hospitalization more easily. IMPLICATIONS FOR PRACTICE: The findings provide information for health professionals to understand children's psychological status during hospitalization and help nurses to plan individualized psychological care for children.
