Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 36
Filter
1.
J Interprof Care ; 37(6): 944-953, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-36883789

ABSTRACT

Interprofessional education (IPE) for patient safety is becoming increasingly important worldwide. However, Korea lacks a systematic approach toward patient safety, despite the high demand for teamwork and patient communication education. This study aims to determine the effectiveness of a patient safety IPE program using medical error scenarios. The program was developed to enhance patient safety motivation and interprofessional learning attitudes among medical and nursing students, and evaluate the design of the program and students' satisfaction levels. The program comprises two modules, each consisting of lectures, team-based case analysis, role-play, and high-fidelity simulation activities. This study followed a quasi-experimental pre-post test design to determine program outcomes. An online survey for the Readiness for Interprofessional Learning Scale (RIPLS), patient safety motivation, program design evaluation, and program satisfaction was conducted before and after the program. Data were analyzed using descriptive statistics, paired sample t-tests, and Pearson's correlation. The pre-post RIPLS and patient safety results were significant (t = -5.21, p < .001;t = -3.20, p = .002). The results of the medical scenario examination of the patient safety IPE program showed improved motivation for patient safety among students, and contributed to the improvement of IPE learning attitudes by improving team work and collaboration.


Subject(s)
Education, Nursing, Baccalaureate , Students, Medical , Students, Nursing , Humans , Patient Safety , Interprofessional Education , Interprofessional Relations , Attitude of Health Personnel , Republic of Korea
2.
Article in English | MEDLINE | ID: mdl-35954597

ABSTRACT

Social isolation and loneliness are the key risk factors for depression in late life. Older adults living alone and socially isolated are at greater risk for physical and mental health. This study aims to examine the mediating effects of subjective physical health, resilience, and social support on the association between loneliness and depression among the elderly female population living alone in South Korea. We included a total of 308 older women aged 60 years or older who live alone in a medium-sized city in South Korea. The survey data was collected using the validated survey instruments between November 2015 and April 2016. A parallel mediation model was performed to investigate whether physical health, resilience, and social support had mediating effects on the association of loneliness with depression. The findings of this study showed that loneliness was directly and indirectly associated with depression through its association with the subjective physical health, resilience, and social support among the older female population living alone. Our results suggest the importance of supporting community-based programs to improve physical and mental health of the elderly people as a way to minimize the level of loneliness and prevent depression.


Subject(s)
Independent Living , Loneliness , Aged , Depression/epidemiology , Depression/psychology , Female , Home Environment , Humans , Loneliness/psychology , Republic of Korea/epidemiology , Social Support
3.
Biochem Biophys Res Commun ; 578: 35-41, 2021 11 12.
Article in English | MEDLINE | ID: mdl-34536827

ABSTRACT

Neuron-restrictive silencing factor (NRSF), also known as RE-1 silencing transcription factor (REST), has pivotal functions in many neuron-specific genes. Previous studies revealed that neuron-specific alternative splicing (AS) of REST produces divergent forms of REST variants and provides regulatory complexity in the nervous system. However, the biological significance of these variants in the regulation of neuronal activities remains to be clarified. Here, we revealed that Charlatan (Chn), a Drosophila REST-like molecule, is also regulated by neuron-specific AS. Neuron-specific AS produced six divergent variants of Chn proteins, one of which preferentially localized to axons. A small sequence of this variant was especially important for the axonal localization. Our data suggest that some variants have roles beyond the transcriptional regulation of neuronal activities.


Subject(s)
Axons/metabolism , Drosophila Proteins/metabolism , Drosophila/genetics , Neurons/metabolism , Repressor Proteins/metabolism , Transcription Factors/genetics , Alternative Splicing , Animals , Drosophila/metabolism , Drosophila Proteins/genetics , Repressor Proteins/genetics , Transcription Factors/metabolism
4.
Adv Exp Med Biol ; 1076: 25-40, 2018.
Article in English | MEDLINE | ID: mdl-29951813

ABSTRACT

Alzheimer's disease (AD) is the most epidemic neuronal dysfunctions among elderly people. It is accompanied by neuronal disorders along with learning and memory defects, as well as massive neurodegeneration phenotype. The presence of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques, called senile plaques (SPs), and brain atrophy are typically observed in the brains of AD patients. It has been over 20 years since the discovery that small peptide, called beta-amyloid (Aß), has pivotal role for the disease formation. Since then, a variety of drugs have been developed to cure AD; however, there is currently no effective drug for the disorder. This therapeutic void reflects lacks of ideal model system, which can evaluate the progression of AD in a short period. Recently, large numbers of AD model system have been established using Drosophila melanogaster by overproducing Aß molecules in the brain. These systems successfully reflect some of the symptoms along with AD. In this review, we would like to point out "pros and cons" of Drosophila AD models.


Subject(s)
Alzheimer Disease , Disease Models, Animal , Drosophila melanogaster , Animals , Humans
5.
Obstet Gynecol Sci ; 60(6): 579-586, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29184867

ABSTRACT

OBJECTIVE: Adenomyosis and endometriosis are relatively common gynecological diseases that exhibit many common features. This study identified gynecological and non-gynecological diseases that exhibited comorbidity with adenomyosis and endometriosis in Korean women. METHODS: We used Health Insurance Review and Assessment data from 2009 to 2011 and searched for adenomyosis and endometriosis (coded as N80.1 and D25 in International Classification of Disease, 10th revision [ICD-10], respectively). We selected records from patients who had independent disease occurrences in each year, and comorbidities were estimated using Fisher's exact test. We computed each year's similarities and combined 3 years' results using Fisher's P-value summation method. RESULTS: A total of 61,516 patients' data were collected during the study period. The prevalence of adenomyosis and endometriosis were similar each year: 12.4% and 9.3% in 2009, 12.5% and 9.4% in 2010 and 13.3% and 9.1% in 2011, respectively. Meta-analysis revealed that 31 ICD-10 codes were significantly related with adenomyosis, and 44 ICD-10 codes were related with endometriosis. Gynecological diseases, such as leiomyoma and benign ovarian tumor, were significantly related to adenomyosis and endometriosis. Non-gynecological diseases, such as anemia and hypercholesterolemia, were also related to adenomyosis and endometriosis. CONCLUSION: We must monitor for the presence of gynecological and non-gynecological diseases with co-morbidities during evaluations and follow-up of patients with adenomyosis or endometriosis.

6.
Hum Mol Genet ; 26(23): 4642-4656, 2017 12 01.
Article in English | MEDLINE | ID: mdl-28973191

ABSTRACT

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. During the progression of AD, massive neuronal degeneration occurs in the late stage of the disease; however, the molecular mechanisms responsible for this neuronal loss remain unknown. AßpE3-42 (an N-terminal-truncated amyloid-ß peptide that begins with pyroglutamate at the third position) is produced during late-stage AD. It also aggregates more rapidly in vitro and exhibits greater toxicity in neurons than full-length Aß1-42. In the present study, we established a Drosophila melanogaster model that expresses Aß3-42E3Q, which effectively produces AßpE3-42, and investigated the function of AßpE3-42 using the photoreceptor neurons of Drosophila. AßpE3-42 induced caspase-dependent apoptosis and caused progressive degeneration in photoreceptor neurons. Mutations in ER stress response genes or the administration of an inhibitor of the ER stress response markedly suppressed the degeneration phenotype, suggesting that the ER stress response plays an important role in neurodegeneration caused by AßpE3-42. We also confirmed that human Tau-dependent apoptotic induction was strongly enhanced by AßpE3-42. Thus, AßpE3-42 expression system in the fly may be a promising new tool for studying late-onset neurodegeneration in AD.


Subject(s)
Amyloid beta-Peptides/biosynthesis , Endoplasmic Reticulum Stress/physiology , Neurodegenerative Diseases/metabolism , Peptide Fragments/biosynthesis , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Animals , Apoptosis/physiology , Brain/metabolism , Caspases/metabolism , Disease Models, Animal , Drosophila Proteins/metabolism , Drosophila melanogaster , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Neurons/metabolism , Neurons/pathology , Peptide Fragments/genetics , Peptide Fragments/metabolism , Pyrrolidonecarboxylic Acid/metabolism
8.
Arch Psychiatr Nurs ; 30(4): 463-9, 2016 08.
Article in English | MEDLINE | ID: mdl-27455919

ABSTRACT

Coping self-efficacy is regarded as an important indicator of the quality of life and well-being for community-dwelling patients with depression. The Depression Coping Self-Efficacy Scale (DCSES) was designed to measure self-efficacy beliefs related to the ability to perform tasks specific to coping with the symptoms of depression. The purpose of this study was to examine the psychometric properties of a Korean version of the Depression Coping Self-Efficacy Scale (DCSES-K) for community-dwelling patients with depression. A cross-sectional survey design was used. Content and semantic equivalence of the instrument using translation and back-translation of the DCSES was established. A convenience sample of 149 community-dwelling patients with depression was recruited from psychiatric outpatient clinics. The reliability alpha for the DCSES-K was .93, and the internal consistency was found to be acceptable. For convergent validity, DCSES-K score was positively correlated with the General Self-Efficacy Scale (GSES-K) score. For construct validity, significant differences in DCSES-K scores were found between a lower BDI group (mean=73.7, SD=16.54) and a higher BDI group (mean=53.74, SD=16.99) (t=7.19, p<.001). For the DCSES-K, 5 factors were extracted, accounting for 62.7% of the variance. Results of this study suggest that DCSES-K can be used as a reliable and valid measure for examining self-efficacy coping with depression for Korean community-dwelling patients with depression.


Subject(s)
Adaptation, Psychological , Psychiatric Status Rating Scales/standards , Self Efficacy , Cross-Sectional Studies , Depression , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales/statistics & numerical data , Psychometrics/statistics & numerical data , Quality of Life , Reproducibility of Results , Translating
9.
Am J Neurodegener Dis ; 5(1): 62-8, 2016.
Article in English | MEDLINE | ID: mdl-27073743

ABSTRACT

Transducin ß-like 1 (TBL1), a transcriptional co-repressor complex, is a causative factor for late-onset hearing impairments. Transcriptional co-repressor complexes play pivotal roles in gene expression by making a complex with divergent transcription factors. However, it remained to be clarified how co-repressor complex regulates cellular survival. We herein demonstrated that ebi, a Drosophila homologue of TBL1, suppressed photoreceptor cell degeneration in the presence of excessive innate immune signaling. We also showed that the balance between NF-κB and AP-1 is a key component of cellular survival under stress conditions. Given that Ebi plays an important role in innate immune responses by regulating NF-κB activity and inhibition of apoptosis induced by associating with AP-1, it may be involved in the regulation of photoreceptor cell survival by modulating cross-talk between NF-κB and AP-1.

10.
Aging (Albany NY) ; 8(3): 427-39, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26959388

ABSTRACT

Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-ß (Aß), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aß-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aß-induced neuronal dysfunction quantitatively over time.


Subject(s)
Alzheimer Disease/complications , Amyloid beta-Peptides/metabolism , Disease Models, Animal , Hair Cells, Auditory/metabolism , Hearing Loss, High-Frequency/etiology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Female , Hair Cells, Auditory/pathology , Hearing Loss, High-Frequency/metabolism , Hearing Loss, High-Frequency/pathology , Male , Mice, Transgenic , tau Proteins/metabolism
11.
Clin Nurs Res ; 25(6): 665-682, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26105189

ABSTRACT

The purpose of this study was to examine a staged theoretical model to explain cultural knowledge-based multidimensional burden of women family caregivers caring for community-dwelling older adults using a modified Poulshock and Deimling model. In the model, the antecedents included elders' impairment in activities of daily living (ADL), elders' cognitive impairment, caregivers' self-efficacy, and caregivers' familism. The perception contained the disruptive behavior burden and social functioning burden of caregivers. The consequence variable included social activity restriction and negative changes in family relationships. The total sample was 157 primary women caregivers caring for community-dwelling older adults aged 65 and older. Instruments were General Self-Efficacy Scale, Family Scale, and Burden Scale. Path analysis was done to analyze the model using multiple linear regression methods. This study showed that impairments of older adults (impairment in ADL, cognitive impairment) and caregiver beliefs (strong familism, low self-efficacy) had an indirect influence on negative changes in family relationship and social activity restriction through the perceived emotional distress.


Subject(s)
Adaptation, Psychological , Caregivers/psychology , Stress, Psychological , Activities of Daily Living , Cognitive Dysfunction , Female , Humans , Independent Living , Models, Theoretical , Republic of Korea , Self Efficacy
12.
PLoS One ; 10(11): e0141457, 2015.
Article in English | MEDLINE | ID: mdl-26524764

ABSTRACT

The innate immune response and stress-induced apoptosis are well-established signaling pathways related to cellular defense. NF-κB and AP-1 are redox-sensitive transcription factors that play important roles in those pathways. Here we show that Ebi, a Drosophila homolog of the mammalian co-repressor molecule transducin ß-like 1 (TBL1), variously regulates the expression of specific genes that are targets of redox-sensitive transcription factors. In response to different stimuli, Ebi activated gene expression to support the acute immune response in fat bodies, whereas Ebi repressed genes that are involved in apoptosis in photoreceptor cells. Thus, Ebi seems to act as a regulatory switch for genes that are activated or repressed in response to different external stimuli. Our results offer clear in vivo evidence that the Ebi-containing co-repressor complex acts in a distinct manner to regulate transcription that is required for modulating the output of various processes during Drosophila development.


Subject(s)
Cell Cycle Proteins/metabolism , Drosophila Proteins/genetics , Drosophila melanogaster/immunology , Fat Body/immunology , GTP-Binding Proteins/metabolism , Animals , Apoptosis , Drosophila Proteins/metabolism , Gene Expression Regulation , Immunity, Innate , Oxidation-Reduction , Photoreceptor Cells, Invertebrate/cytology , Promoter Regions, Genetic , Signal Transduction , Transcription, Genetic
13.
Dev Growth Differ ; 56(5): 358-67, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24738783

ABSTRACT

Neuronal network consists of many types of neuron and glial cells. This diversity is guaranteed by the constant cell proliferation of neuronal stem cells following stop cell cycle re-entry, which leads to differentiation during development. Neuronal differentiation occurs mainly at the specific cell cycle phase, the G1 phase. Therefore, cell cycle exit at the G1 phase is quite an important issue in understanding the process of neuronal cell development. Recent studies have revealed that aberrant S phase re-entry from the G1 phase often links cellular survival. In this review we discuss the different types of G1 arrest on the process of neuronal development in Drosophila. We also describe the issue that aberrant S phase entry often causes apoptosis, and the same mechanism might contribute to sensory organ defects, such as deafness.


Subject(s)
Drosophila/cytology , Drosophila/metabolism , Animals , Apoptosis , Cell Cycle , Cell Cycle Proteins/metabolism , Cell Survival , Drosophila/embryology , Drosophila Proteins/metabolism , G1 Phase , GTP-Binding Proteins/metabolism , Humans , Models, Animal , Neurogenesis , S Phase
14.
Am J Neurodegener Dis ; 3(3): 134-42, 2014.
Article in English | MEDLINE | ID: mdl-25628964

ABSTRACT

Aging is a major risk factor for Alzheimer's disease (AD). Aggregation of amyloid beta (Aß) in cerebral cortex and hippocampus is a hallmark of AD. Many factors have been identified as causative elements for onset and progression of AD; for instance, tau seems to mediate the neuronal toxicity of Aß, and downregulation of macroautophagy (autophagy) is thought to be a causative element of AD pathology. Expression of autophagy-related genes is reduced with age, which leads to increases in oxidative stress and aberrant protein accumulation. In this study, we found that expression of the autophagy-related genes atg1, atg8a, and atg18 in Drosophila melanogaster was regulated with aging as well as their own activities. In addition, the level of atg18 was maintained by dfoxo (foxo) and dsir2 (sir2) activities in concert with aging. These results indicate that some autophagy-related gene expression is regulated by foxo/sir2-mediated aging processes. We further found that reduced autophagy activity correlated with late-onset neuronal dysfunction caused by neuronal induction of Aß. These data support the idea that age-related dysfunction of autophagy is a causative element in onset and progression of AD.

15.
Genes Cells ; 18(11): 934-45, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23919485

ABSTRACT

The IMD pathway is one of the major regulators of the innate immune response in Drosophila. Although extensive analysis of the IMD pathway has been carried out, precise mechanisms for how each target gene of the pathway is down-regulated remain to be clarified. Here, we carried out genetic screening and found that fat facets (faf), which encodes a deubiquitinating enzyme, inhibited the expression of the target genes of the IMD pathway. Overexpression of faf suppressed the infection-induced expression of Diptericin and increased susceptibility to bacterial infection in flies, whereas faf loss-of-function mutants decreased susceptibility. Time course analysis revealed that specific subsets of the target genes of the IMD pathway were affected by faf. Biochemical analysis showed that Faf made a complex with Imd, and both Faf and Imd were polyubiquitinated when they were co-overexpressed. Given that faf-dependent Imd polyubiquitination did not seem to cause protein degradation of Imd, Faf might inhibit the IMD pathway by modulating the state of Imd ubiquitination and/or stability.


Subject(s)
Drosophila Proteins/metabolism , Drosophila/immunology , Endopeptidases/metabolism , Adenosine Monophosphate/genetics , Adenosine Monophosphate/metabolism , Animals , Bacillus subtilis , Drosophila/metabolism , Drosophila/microbiology , Endopeptidases/genetics , Enterobacter cloacae , Immunity, Innate , Mutation , Signal Transduction , Ubiquitination
16.
Genes Cells ; 18(11): 909-20, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23919509

ABSTRACT

As multicellular organisms develop, many cells permanently stop dividing and undergo terminal differentiation. The G1 phase of the cell cycle is thought to be the critical decision point for differentiation. Many growth factors, such as epidermal growth factor, are involved in regulating the G1 to S phase transition, and aberrant activation of growth factor signaling is one of the critical causes of tumor formation. Therefore, each cell must have proper mechanisms to suppress inappropriate/excessive activation of growth factor signaling, but the underlying molecular mechanisms remain undefined. Here, we found that ebi, a Drosophila homologue of genes encoding transducin-ß-like 1 and transducin-ß-like 1-related protein, mitigated excess growth stimulation by taking advantage of its distinct epigenetic functions. Ebi acted as a corepressor of transcription by forming a complex with retinoblastoma family protein (RBF), a Drosophila homologue of retinoblastoma, and regulating the expression of specific target genes of the Rbf/E2F pathway. Furthermore, ebi also sustained expression of certain genes, including Rbf, encoding factors that inhibit progression out of G1. Our genetic studies suggest that the antagonistic function of ebi against the Polycomb group silencing complex plays a role in the G1/S phase transition.


Subject(s)
Cell Cycle Proteins/metabolism , Drosophila Proteins/metabolism , Drosophila/growth & development , Epigenesis, Genetic , GTP-Binding Proteins/metabolism , Animals , Cell Cycle Proteins/genetics , Compound Eye, Arthropod/growth & development , Compound Eye, Arthropod/metabolism , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/genetics , ErbB Receptors/genetics , Eye Proteins/metabolism , G1 Phase , GTP-Binding Proteins/genetics , Gene Expression Regulation, Developmental , Polycomb-Group Proteins/antagonists & inhibitors , Retinoblastoma Protein/metabolism , S Phase , Signal Transduction , Transcription Factors/metabolism , Transcription, Genetic
17.
Int J Nurs Pract ; 18(5): 481-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23009377

ABSTRACT

The purpose of the study was to determine home environmental and health-related factors among home fallers and recurrent fallers in community dwelling older Korean women. The study population included 438 older women aged 65 years and over. Measures included a checklist of home environments and health-related items. Risk indicators for accidental falls and recurrent falling were analysed using logistic regression. Logistic regression analysis revealed that chronic disease (odds ratio (OR) = 2.02, P = 0.007), poor night light (OR = 1.97, P = 0.032) and obstacle of door sill (OR = 1.76, P = 0.021) were predictors of accidental falls, and physical inactivity (OR = 2.34, P = 0.018) and slippery floor in the bathroom (OR = 0.41, P = 0.034) were predictors of recurrent falling. The findings have implications for strategies and suggest the need to modify home environmental context in systematic and consistent ways and the need to maintain physical activities to prevent falls and recurrent falling.


Subject(s)
Accidental Falls/prevention & control , Accidents, Home/prevention & control , Health Status , Residence Characteristics , Accidental Falls/statistics & numerical data , Accidents, Home/statistics & numerical data , Aged , Aged, 80 and over , Chronic Disease/epidemiology , Female , Humans , Logistic Models , Prevalence , Recurrence , Republic of Korea/epidemiology , Risk Factors
18.
J Clin Nurs ; 21(15-16): 2377-85, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22788568

ABSTRACT

AIMS AND OBJECTIVES: To test a staged theoretical model designed to explain causal relationships affecting the quality of life (QOL) of middle-aged Korean women suffering from Hwa-Byung (HB). BACKGROUND: The model contains three stages comprised of antecedents (stage 1), perception (stage 2) and outcome variable (stage 3). Stage 1 contains individual characteristic and emotional distress variables. In stage 2, the perception variable is depression (DEP). In stage 3, the outcome factor is QOL. Design. A cross-sectional, descriptive design was used. METHODS: A convenience sample of 135 community dwelling middle-aged women was recruited over a five-month period in the neuropsychology outpatient clinic at an Oriental hospital in Korea. The instruments were the Korean version of WHO Quality of Life-BREF (WHOQOL-BREF), Korean version of State-Trait Anger Expression Inventory (STAXI-K), The Korean version of State-Trait Anxiety Inventory (STAI-K) and Korean version of Beck Depression Inventory (K-BDI). RESULTS: Forty-five per cent of the variance in the QOL of women with HB was explained by the direct effect of depression (ß = -0·356, p = 0·000) and trait anxiety (ß = -0·324, p = 0·001). State anger (ß = 0·429, p = 0·000) and spouse (ß = -0·180, p = 0·021) explained 45·0% of the variance in (of) depression. CONCLUSION: The findings showed that depression mediates the relationship between the emotional distress and QOL as a negative outcome. RELEVANCE TO CLINICAL PRACTICE: These relationships can guide researchers and psychiatric mental health nurses to understand depression as a mediating factor and to develop nursing interventions to improve QOL of HB women.


Subject(s)
Anger , Hostility , Quality of Life/psychology , Adult , Anxiety Disorders/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Middle Aged , Models, Theoretical , Republic of Korea/epidemiology , Surveys and Questionnaires
19.
PLoS One ; 7(5): e37028, 2012.
Article in English | MEDLINE | ID: mdl-22666340

ABSTRACT

Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin ß-like protein 1 (TBL1) is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1) and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.


Subject(s)
Apoptosis/genetics , Cell Cycle Proteins/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Drosophila melanogaster/metabolism , GTP-Binding Proteins/metabolism , Gene Silencing , Photoreceptor Cells/cytology , Transcription Factor AP-1/metabolism , Animals , Binding Sites , Cell Cycle Proteins/chemistry , Cell Cycle Proteins/genetics , Cell Survival/genetics , Drosophila Proteins/chemistry , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , GTP-Binding Proteins/chemistry , GTP-Binding Proteins/genetics , Male , Neuropeptides/genetics , Photoreceptor Cells/metabolism , Promoter Regions, Genetic/genetics , Retinal Degeneration/genetics , Retinal Degeneration/metabolism , Retinal Degeneration/pathology , Sequence Deletion , Time Factors
20.
Aging (Albany NY) ; 3(11): 1098-109, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22156377

ABSTRACT

The O-type forkhead domain transcription factor (FOXO) is involved in many biological processes such as aging, the oxidative stress response, and growth regulation. FOXO activity is tightly controlled within cells. In particular, growth factor signaling pathways and the oxidative stress response can both stimulate nuclear translocation of this transcription factor. Here, we show that tetrahydrocurcumin (THC), a curcumin metabolite, regulates the oxidative stress response and aging via FOXO. In NIH3T3 cells, THC induced nuclear accumulation of FOXO4, a member of the FOXO family of transcription factors, by inhibiting phosphorylation of protein kinase B (PKB)/Akt. In Drosophila melanogaster, THC attenuated the oxidative stress response, an effect that was blocked in a foxo mutant background. THC also extended the life span of Drosophila under normal conditions, and loss of either foxo or Sir2 activity eliminated this effect. Based on these results, THC may regulate the aging process via an evolutionarily conserved signaling pathway that includes both foxo and Sir2.


Subject(s)
Curcumin/analogs & derivatives , Forkhead Transcription Factors/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , Signal Transduction/physiology , Animals , Blotting, Western , Curcumin/pharmacology , Drosophila melanogaster , Immunohistochemistry , Life Expectancy , Mice , NIH 3T3 Cells , Oxidative Stress/physiology
SELECTION OF CITATIONS
SEARCH DETAIL