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1.
J Biol Chem ; 289(37): 25797-811, 2014 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-25077971

RESUMO

Phosphodiesterases (PDEs) play key roles in cAMP compartmentalization, which is required for intracellular signaling processes, through specific subcellular targeting. Previously, we showed that the long and short forms of Aplysia PDE4 (ApPDE4), which are localized to the membranes of distinct subcellular organelles, play key roles in 5-hydroxytryptamine-induced synaptic facilitation in Aplysia sensory and motor synapses. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, we further investigated the molecular mechanism of the membrane targeting of the ApPDE4 long and short forms. We found that the membrane targeting of the long form was mediated by hydrophobic interactions, mainly via 16 amino acids at the N-terminal region, whereas the short form was targeted solely to the plasma membrane, mainly by nonspecific electrostatic interactions between their N termini and the negatively charged lipids such as the phosphatidylinositol polyphosphates PI4P and PI(4,5)P2, which are embedded in the inner leaflet of the plasma membrane. Moreover, oligomerization of the long or short form by interaction of their respective upstream conserved region domains, UCR1 and UCR2, enhanced their plasma membrane targeting. These results suggest that the long and short forms of ApPDE4 are distinctly targeted to intracellular membranes through their direct association with the membranes via hydrophobic and electrostatic interactions, respectively.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Aplysia/enzimologia , Isoformas de Proteínas/metabolismo , Sinapses/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/genética , Sequência de Aminoácidos , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Membranas Intracelulares/efeitos dos fármacos , Isoformas de Proteínas/genética , Multimerização Proteica/genética , Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sinapses/genética
2.
Ann Occup Environ Med ; 34: e23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267357

RESUMO

Background: The musculoskeletal disease (MSD) burden is an important health problem among Korean fishers. We aimed to investigate the indicators of the prevalence of MSD and contributions of significant indicators to MSD in Korean fishers. Methods: This cross-section study included 927 fishers (male, 371; female, 556) aged 40 to 79 years who were enrolled from 3 fishery safety and health centers. The outcome variable was one-year prevalence of MSD in 5 body parts (the neck, shoulder, hand, back, and knee). Independent variables were sex, age, educational attainment, household income, job classification, employment xlink:type, hazardous working environment (cold, heat, and noise), ergonomic risk by the 5 body parts, anxiety disorder, depression, hypertension, diabetes, and hyperlipidemia. The adjusted odds ratio of MSDs by the 5 body parts were calculated using multiple logistic regression analysis. We computed the population attributable fraction (PAF) for each indicators of MSDs using binary regression models. Results: The one-year prevalence of MSD in the neck, shoulder, hand, back, and knee was 7.8%, 17.8%, 7.8%, 27.2%, and 16.2% in males vs. 16.4%, 28.1%, 23.0%, 38.7%, and 30.0% in females, respectively. The ergonomic risk PAF according to the body parts ranged from 22.8%-59.6% in males and 22.8%-50.3% in female. Mental diseases showed a significant PAF for all body parts only among female (PAF 9.1%-21.4%). Cold exposure showed a significant PAF for the neck, shoulder, and hand MSD only among female (25.6%-26.8%). Age was not a significant indicator except for the knee MSD among female. Conclusions: Ergonomic risk contributed majorly as indicators of MSDs in both sexes of fishers. Mental disease and cold exposure were indicators of MSDs only among female fishers. This information may be important for determining priority risk groups for the prevention of work-related MSD among Korean fishers.

3.
Ann Occup Environ Med ; 34: e38, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36544890

RESUMO

Background: This study investigated the risk perceptions, prevalence of environmental diseases (EDs) and associated factors with the prevalence of environmental disease among the population living near an incinerator. Methods: Study area were divided into 3 local areas near the incinerator by distance (A, B, C) and control area (D) by distance and geographic isolation. A Questionnaire was conducted with 1,380 in local residents (A, B, C) and 390 in control area (D), gathered information of demographic characteristics, lifestyle, perception of damage by incinerators, experience of EDs (atopic dermatitis, allergic rhinitis, asthma) diagnosed by physician. Analysis of variance, χ2 test, and Kruskal Wallis test was applied to determine the difference by area. Logistic regression analysis was performed to identify factors associated with the prevalence of allergic rhinitis. Results: Residents residing closer to the incinerator had negative perception in most items in questionnaire compared with control. The prevalence of allergic rhinitis was higher as they lived nearby the incinerator (p = 0.008). The associated factors with the prevalence of allergic rhinitis were carpet (odds ratio [OR]: 1.79, p = 0.001), residential area (marginally significant), duration of residence (OR: 1.09, p < 0.001). The perception of environmental pollution around the residential area was inversely associated with the prevalence of allergic rhinitis: perceived as very dissatisfied (OR: 4.21, p = 0.02) compared with very satisfied. Conclusions: As closer to the incinerator, the risk perception tend to negative and prevalence of EDs were increased. Carpet, residential area, duration of residence and perception of environmental air pollution around the residential area were associated with prevalence of allergic rhinitis. These results may be useful for the communication with residents to discuss the environmental problems caused by the incinerator.

4.
BMB Rep ; 54(2): 118-123, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33298241

RESUMO

The bacterial effector protein RavZ from a pathogen can impair autophagy in the host by delipidating the mammalian autophagy- related gene 8 (mATG8)-phosphatidylethanolamine (PE) on autophagic membranes. In RavZ, the membrane-targeting (MT) domain is an essential function. However, the molecular mechanism of this domain in regulating the intracellular localization of RavZ in cells is unclear. In this study, we found that the fusion of the green fluorescent protein (GFP) to the MT domain of RavZ (GFP-MT) resulted in localization primarily to the cytosol and nucleus, whereas the GFP-fused duplicated-MT domain (GFP-2xMT) localized to Rab5- or Rab7-positive endosomes. Similarly, GFP fusion to the catalytic domain (CA) of RavZ (GFP-CA) resulted in localization primarily to the cytosol and nucleus, even in autophagy-induced cells. However, by adding the MT domain to GFP-CA (GFP-CA-MT), the cooperation of MT and CA led to localization on the Rab5-positive endosomal membranes in a wortmannin-sensitive manner under nutrient-rich conditions, and to autophagic membranes in autophagy-induced cells. In autophagic membranes, GFP-CA-MT delipidated overexpressed or endogenous mATG8-PE. Furthermore, GFP-CAΔα3-MT, an α3 helix deletion within the CA domain, failed to localize to the endosomal or autophagic membranes and could not delipidate overexpressed mATG8-PE. Thus, the CA or MT domain alone is insufficient for stable membrane localization in cells, but the cooperation of MT and CA leads to localization to the endosomal and autophagic membranes. In autophagic membranes, the CA domain can delipidate mATG8-PE without requiring substrate recognition mediated by LC3-interacting region (LIR) motifs. [BMB Reports 2021; 54(2): 118-123].


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Endossomos/metabolismo , Membranas Intracelulares/metabolismo , Autofagia , Domínio Catalítico , Proteínas de Fluorescência Verde/metabolismo , Humanos
5.
Psychiatry Investig ; 17(2): 163-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32093460

RESUMO

OBJECTIVE: For the proper treatment of first-episode psychosis, assessment of treatment response, remission, relapse, and recovery is important. Therefore, the present study aimed to develop operational definitions of clinical outcomes in first-episode psychosis. METHODS: A questionnaire was developed by a panel of experts and underwent three revisions. The final survey was presented to 150 psychiatrists who were members of the Korean Society for Schizophrenia Research. Respondents selected factors that they believed were important to consider while defining treatment response, remission, relapse, and recovery using a 6-point Likert scale. Selected factors that constituted each definition were statistically extracted, and operational definitions were developed. RESULTS: A total of 91 experts responded to the survey. The extent of reduction in psychopathology, socio-occupational functioning, and duration of each state were the core factors of each definition. Outcomes obtained from discussions and consultations by experts have been summarized and proposed. CONCLUSION: The criteria developed in this survey tended to be somewhat stricter than those used by other studies. The fundamental reason for this is that this survey focused on first-episode psychosis. A better understanding of each definition in first-episode psychosis is necessary to improve effective treatment outcomes.

6.
Breast Cancer Res Treat ; 115(3): 497-503, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18982444

RESUMO

The objective of this review was to assess the effectiveness of acupuncture as a treatment option for hot flashes in patients with breast cancer. We searched the literature using 14 databases from their inceptions to August 2008, without language restrictions. We included randomised clinical trials (RCTs) comparing real with sham acupuncture or another active treatment or no treatment. Their methodological quality was assessed using the modified Jadad score. Three RCTs compared the effects of manual acupuncture with sham acupuncture. One RCT showed favourable effects of acupuncture in reducing hot flash frequency, while other two RCTs failed to do so. The meta-analysis show significant effects of acupuncture compared with sham acupuncture (n = 189, weight mean difference, 3.09, 95% confidence intervals -0.04 to 6.23, P = 0.05) but marked heterogeneity was observed in this model (chi (2) = 8.32, P = 0.02, I (2) = 76%). One RCT compared the effects of electroacupuncture (EA) with hormone replacement therapy. Hormone therapy was more effective than EA. Another RCT compared acupuncture with venlafaxine and reported no significant intergroup difference. A further RCT compared acupuncture with applied relaxation and failed to show a significant intergroup difference. In conclusion, the evidence is not convincing to suggest acupuncture is an effective treatment of hot flash in patients with breast cancer. Further research is required to investigate whether there are specific effects of acupuncture for treating hot flash in patients with breast cancer.


Assuntos
Terapia por Acupuntura , Neoplasias da Mama/terapia , Fogachos/terapia , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Support Care Cancer ; 17(7): 763-70, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19224253

RESUMO

GOALS OF WORK: The goal of the study was to assess the effects of acupuncture as a treatment for hot flushes in prostate cancer (PC) patients. MATERIALS AND METHODS: The literature was searched using 14 databases with dates ranging from their inceptions to December 2008 and without language restrictions. All clinical studies of any type of acupuncture in PC patients were included. Their main outcome measures had to be vasomotor symptoms. Their methodological quality was assessed using the modified Jadad score. RESULTS: Six studies met all the inclusion criteria. One randomised clinical trial compared the effects of manual acupuncture with acupuncture plus electro-acupuncture. The other five studies were uncontrolled observational studies and therefore had limitations. CONCLUSION: The evidence is not convincing to suggest acupuncture is an effective treatment for hot flush in patients with PC. Further research is required to investigate whether acupuncture has hot-flush-specific effects.


Assuntos
Terapia por Acupuntura/métodos , Fogachos/terapia , Neoplasias da Próstata/terapia , Ensaios Clínicos como Assunto , Eletroacupuntura/métodos , Fogachos/etiologia , Humanos , Masculino
8.
Ann Occup Environ Med ; 30: 23, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29713476

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) produced by incomplete combustion have negative effects on human health due to their carcinogenicity and teratogenicity. Indoor sources of PAHs include tobacco smoke, heating sources, and cooking. This study evaluated the relationship between human PAH exposure and residence characteristics. METHOD: This study was based on the second Korean National Environmental Health Survey (2012-2014). Non-smoking housewives were included in the analyses (n = 1269). The concentrations of urinary PAH metabolites (2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene) were adjusted by urine creatinine level. The geometric mean concentrations of urinary PAH metabolites by residential factors were examined. Logistic regression models were used to evaluate associations between residential variables and PAH exposures. RESULTS: The adjusted geometric mean concentrations of urinary 2-hydroxyfluorene and 1-hydroxyphenanthrene were significantly higher in the group residing within 100 m of a major road (p < 0.05) than in those residing > 100 m from a major road. In logistic regression analyses, the odds ratio (OR) for exceeding the third quartile of urinary 1-hydroxypyrene concentration was significantly higher in the group using coal or wood fuel for residential heating than in the group using gas (OR = 2.745, 95% confidence interval [CI] = 1.295-5.819). The detached house group had a significantly higher OR for 1-hydroxyphenanthrene compared with the apartment group (OR = 1.515, 95% CI = 1.023-2.243). CONCLUSION: Our study shows the evidence of associations between some urinary PAH metabolite levels (1-hydroxyphenanthrene and 1-hydroxypyrene) and residence characteristics. Additional studies are needed to clarify these associations.

9.
Ann Occup Environ Med ; 29: 23, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652920

RESUMO

BACKGROUND: Occupational physicians (OPs) have complex relationships with employees, employers, and the general public. OPs may have simultaneous obligations towards third parties, which can lead to variable conflicts of interests. Among the various studies of ethical issues related to OPs, few have focused on the Korean OPs. The aim of the present survey was to investigate the ethical contexts, the practical resolutions, and the ethical principles for the Korean OPs. METHODS: An email with a self-administered questionnaire was sent to members of the Korean Society of Occupational and Environmental Medicine, comprising 150 specialists and 130 residents. The questionnaire was also distributed to 52 specialists and 46 residents who attended the annual meeting of the Korean Association of Occupational and Environmental Clinics in October 2015, and to 240 specialists by uploading the questionnaire to the online community 'oem-doctors' in February 2016. The responses to each question (perception of general ethical conflicts, recognition of various ethical codes for OPs, core professional values in ethics of occupational medicine, and a mock case study) were compared between specialists and residents by the chi-squared test and Fisher's exact test. RESULTS: Responses were received from 80 specialists and 71 residents. Most participants had experienced ethical conflicts at work and felt the need for systematic education and training. OPs suffered the most ethical conflicts in decisions regarding occupational health examination and evaluation for work relatedness. Over 60% of total participants were unaware of the ethical codes of other countries. Participants thought 'consideration of worker's health and safety' (26.0%) and 'neutrality' (24.7%) as the prominent ethical values in professionality ofoccupational medicine. In mock cases, participants chose beneficence and justice for fitness for work and confidential information acquired while on duty, and beneficence and respect for autonomy in pre-placement examinations. CONCLUSIONS: This study evaluated the current perception of and attitude toward ethical issues among the Korean OPs. These findings will facilitate the development of a code of ethics and the ethical decision-making program forthe Korean OPs.

10.
Ann Occup Environ Med ; 29: 24, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652921

RESUMO

BACKGROUND: There are few published studies on the relationship between occupational lumbar load and facet joint degeneration (FJD). This cross-sectional study was conducted to evaluate the effect of physical lumbar load on FJD by comparing magnetic resonance imaging (MRI) findings of firefighters (FFs) and hospital office workers (HOWs). METHODS: We randomly sampled 341 male FFs and 80 male HOWs by age stratification. A questionnaire and clinical examination, including MRI of the lumbar spine (T12-S1), were conducted. FJD was diagnosed and graded by using the classification of Pathria et al., and reclassified into two groups as follows: no FJD (grade 0) and FJD (grades 1, 2, and 3). The prevalence of FJD was analyzed according to occupational group. RESULTS: The prevalence of FJD ranged from 31% (L1-L2) to 75% (L4-L5) in the FFs, and from 18% (L1-L2) to 69% (L4-L5) in the HOWs. After adjustment for age, body mass index, and frequency of physical exercise, the adjusted odds ratios (OR) for FJD in the FFs were significantly higher than those in the HOWs at all lumbar spinal levels, except for L3-L4 (L1-L2: OR, 2.644; 95% confidence interval [CI], 1.317-5.310; L2-L3: OR, 2.285; 95% CI, 1.304-4.006; L4-L5: OR, 1.918; 95% CI, 1.037-3.544; L5-S1: OR, 1.811; 95% CI, 1.031-3.181). CONCLUSION: This study shows that FFs exhibit a greater likelihood of having FJD than HOWs after controlling for other risk factors of FJD. This suggests that the physical occupational demands of FFs affect their risk of developing FJD.

11.
Cell Rep ; 20(2): 356-369, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28700938

RESUMO

Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway.


Assuntos
Dendritos/metabolismo , Dendritos/patologia , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Peptídeos/toxicidade , Animais , Proteína de Ligação a CREB/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Imunoprecipitação da Cromatina , Proteína A de Ligação a Elemento de Resposta do AMP Cíclico/metabolismo , Dendritos/efeitos dos fármacos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Neurônios/efeitos dos fármacos
12.
Ann Occup Environ Med ; 28: 69, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27980794

RESUMO

BACKGROUND: This study aimed to investigate the effects of shift work on abdominal obesity among young and middle-aged female nurses during a 5-year retrospective study. METHODS: This retrospective study included female nurses (20-39 years old) who worked at a university hospital in Korea and had available health screening results from 2010-2015. Among 2,611 employees, 934 healthy 20-39-year-old female nurses were identified, and data regarding their demographic information (age and date of employment), waist circumferences (WC), and lifestyle factors (alcohol and exercise) were obtained. Abdominal obesity was defined as a WC of ≥80 cm, based on the World Health Organization's Asia-West Pacific standard in 2000. The mean WC change from baseline was analyzed using the paired t test, and the association between shift work and abdominal obesity was analyzed using the generalized estimating equation. RESULTS: Compared to all day workers (both age groups), the 20-29-year-old nurses did not exhibit significant changes in WC at each follow-up. However, among the 30-39-year-old nurses, shift workers exhibited a significant change in WC (vs. baseline) during years 4 and 5, compared to day workers. After adjusting for effective confounders and stratifying the participants according to age, the 20-29-year-old nurses exhibited an odds ratio of 3.21 (95 % confidence interval: 1.29-7.98) for shift work-associated obesity, although the odds ratio for the 30-39-year-old nurses was not statistically significant. CONCLUSION: In the study population, shift work was associated with a significant change in mean WC among 30-39-year-old nurses, and the shift work-associated risk of abdominal obesity was significant among 20-29-year-old nurses. These results indicate that shift work may influence abdominal obesity differently in 20-29-year-old and 30-39-year-old female nurses.

13.
Asia Pac J Clin Nutr ; 25(2): 340-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27222418

RESUMO

This study investigated the concentration of total mercury (THg) in maternal blood, cord blood, and breast milk, and its association with dietary factors. A total of 127 pregnant women in Busan, Korea were recruited. Maternal blood, cord blood, and breast milk were collected at 36 weeks of gestation, at delivery, and at one week after birth, respectively. Information about dietary habits and other factors were obtained from each subject. The mean THg concentrations in maternal blood, cord blood, and breast milk were 3.12±1.36 µg/L, 5.46±2.41 µg/L, and 0.91±2.08 µg/L, respectively. Positive correlations were found between log-transformed THg concentrations in maternal blood and cord blood (r=0.829, p<0.001), and between maternal blood and breast milk (r=0.296, p=0.001). Multiple linear regression analysis showed that the log-transformed concentration of THg in maternal blood was positively correlated with fish consumption (ß=0.345, p<0.0001) and negatively correlated with bean consumption (ß=-0.055, p=0.048). Fish consumption (ß=0.482, p<0.0001) and maternal age (ß=0.025, p=0.033) were positively associated with the concentration of THg in cord blood, while negative correlations were found for bean consumption (ß=-0.134, p=0.027) and parity (ß=-0.172, p=0.015). Beef consumption (ß=0.031, p=0.007) was positively associated with log-transformed THg concentrations in breast milk, while negative correlations were found for bean consumption (ß=-0.019, p=0.003) and maternal age (ß=-0.083, p=0.004). Our study found that both the dietary and demographic factors differently affected to THg concentrations among samples of maternal blood, cord blood, and breast milk.


Assuntos
Dieta/efeitos adversos , Comportamento Alimentar , Sangue Fetal/química , Mercúrio/sangue , Leite Humano/química , Mães , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem
14.
BMJ Open ; 6(6): e011587, 2016 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-27354080

RESUMO

OBJECTIVES: The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. METHODS: Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. RESULTS: Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of ß (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4-5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). CONCLUSIONS: Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4-5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4-5.


Assuntos
Bombeiros , Degeneração do Disco Intervertebral/epidemiologia , Vértebras Lombares/fisiopatologia , Doenças Profissionais/epidemiologia , Adulto , Distribuição por Idade , Estudos Transversais , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Modelos Logísticos , Dor Lombar/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico por imagem , República da Coreia/epidemiologia , Índice de Gravidade de Doença , Distribuição por Sexo , Inquéritos e Questionários
15.
Aging Cell ; 15(2): 380-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26799631

RESUMO

Hippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age-associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR-204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR-204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR-204 also decreased the total expression of NR1. miR-204 induces senescence-like phenotype in fully matured neurons as evidenced by an increase in p16-positive cells. We suggest that aging is accompanied by the upregulation of miR-204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age-associated decline in hippocampal synaptic plasticity and the related cognitive functions.


Assuntos
Envelhecimento/metabolismo , Hipocampo/metabolismo , MicroRNAs/metabolismo , Neurônios/metabolismo , Receptor EphB2/metabolismo , Envelhecimento/genética , Animais , Regulação para Baixo , Hipocampo/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/biossíntese , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal , Neurônios/citologia , Receptor EphB2/genética , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais
16.
Ann Occup Environ Med ; 27: 14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25992299

RESUMO

OBJECTIVES: Asian migrant workers in Korea have various ethnicities. The purpose of this study was to evaluate the difference in spirometric interpretation made using the set of third National Health and Nutrition Examination Survey (NHANES III) reference equations and the relevant ethnicity-specific reference sets. METHODS: Spirometry was performed on 166 migrant and 498 Korean male workers between March and November 2012. We analyzed the spirometric data of healthy never-smokers. Spirometric patterns were evaluated using the NHANES III reference set and some relevant ethnicity-specific equations (Eom's equation for Koreans, Ip's equation for East Asians, Crapo's equation for Central Asians, Memon's equation for South Asians, and Gnanou's equation for Southeast Asian people). RESULTS: In all migrant groups except the Central Asian group, the forced expiratory volume in 1 second percentage (FEV1%) and forced vital capacity percentage (FVC%) calculated using each of the ethnicity-specific reference equations considered were significantly higher than those calculated using the NHANES III reference set. This study showed that in the evaluation of the spirometric result of subjects from Southeast Asia or South Asia, the percentage of cases with an abnormal FEV1 or FVC increased when the NHANES III set of equations was used as compared to when the ethnicity-specific equations were used. CONCLUSIONS: We found that the spirometric results of all ethnic groups were higher and the composition of the abnormal spirometric result was lower when the ethnicity-specific reference equations were used instead of the NHANES III reference set.

17.
Lipids ; 50(4): 427-36, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25688026

RESUMO

Specific protein-phosphoinositide (PI) interactions are known to play a key role in the targeting of proteins to specific cellular membranes. Investigation of these interactions would be greatly facilitated if GFP-fusion proteins expressed in mammalian cells and used for their subcellular localization could also be employed for in vitro lipid binding. In this study, we found that lysates of cells overexpressing GFP-fusion proteins could be used for in vitro protein-PI binding assays. We applied this approach to examine the PI-binding properties of Aplysia Sec7 protein (ApSec7) and its isoform ApSec7(VPKIS), in which a VPKIS sequence is inserted into the PH domain of ApSec7. EGFP-ApSec7 but not EGFP-ApSec7(VPKIS) did specifically bind to PI(3,4,5)P3 in an in vitro lipid-coated bead assay. Overexpression of EGFP-ApSec7 but not EGFP-ApSec7(VPKIS) did induce neurite outgrowth in Aplysia sensory neurons. Structure modeling analysis revealed that the inserted VPKIS caused misfolding around the PI(3,4,5)P3-binding pocket of ApSec7 and disturbed the binding of PI(3,4,5)P3 to the pleckstrin homology (PH) domain. Our data indicate that plasma membrane localization of EGFP-ApSec7 via the interaction between its PH domain and PI(3,4,5)P3 might play a key role in neurite outgrowth in Aplysia.


Assuntos
Proteínas de Fluorescência Verde/metabolismo , Fosfatidilinositóis/metabolismo , Sequência de Aminoácidos , Animais , Aplysia/citologia , Aplysia/genética , Aplysia/metabolismo , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
18.
Ann Occup Environ Med ; 27: 17, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26120472

RESUMO

OBJECTIVES: To identify any association between implementing smoking regulation policies and workers' urine cotinine concentration levels in Korea. METHODS: From the first stage of the Korean National Environmental Health Survey conducted by the National Institute of Environmental Research from 2009 to 2011, 2,475 non-smoking workers selected. We analyzed the trend in the changes of cotinine concentration in urine using the general linear model and linear regression, in various jobs as categorized by the National Center for Health Statistics (NCHS) and Korea Standard Classification of Occupations (KSCO). RESULTS: The urine cotinine concentration tended to decrease every year (2.91 ng/ml in 2009, 2.12 ng/ml in 2010, and 1.31 ng/ml in 2011), showing a decreasing trend (P < 0.001). The total subjects' decreased cotinine concentration in urine between 2009 and 2011 was 2.72 ng/ml (54.1 % relative decrease). The changes in each subgroup's urine cotinine concentration ranged from 1.59 to 6.03 ng/ml (33.2 to 77.5 %). All groups except for the managerial group (n = 49), which had a small sample size, had statistically significant negative regression coefficients (p < 0.05). The ranges of the decrease in urine cotinine were 2.75 ng/ml (53.6 %) for males and 2.72 ng/ml (54.9 %) for females. The negative slope in urine cotinine level was statistically significantly greater in men than women. The changes in urine cotinine by occupation as classified by the NCHS occupational categories ranged from 2.43 to 3.36 ng/ml (46.6 to 61.5 % relative decrease). The negative slopes in urine cotinine levels of the white-collar and farm workers were statistically significantly greater than those of the service workers and blue-collar workers. The change by occupation as classified by the KSCO ranged from 1.59 to 6.03 ng/ml (a 33.2 to 77.5 % relative decrease). The negative slopes in urine cotinine levels of the professionals and related workers and clerks were statistically significantly greater than those of the service workers and plant and machine operators and assemblers. CONCLUSIONS: The cotinine concentration in urine among non-smoking worker groups tended to decline from 2009 to 2011. Such a result may be an indirect indicator of the effectiveness of smoking regulation policies including the revision of the National Health Promotion Act.

19.
BMB Rep ; 47(10): 563-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24499674

RESUMO

Human genome projects have enabled whole genome mapping and improved our understanding of the genes in humans. However, many unknown genes remain to be functionally characterized. In this study, we characterized human chromosome 4 open reading frame 34 gene (hC4orf34). hC4orf34 was highly conserved from invertebrate to mammalian cells and ubiquitously expressed in the organs of mice, including the heart and brain. Interestingly, hC4orf34 is a novel ER-resident, type I transmembrane protein. Mutant analysis showed that the transmembrane domain (TMD) of hC4orf34 was involved in ER retention. Overall, our results indicate that hC4orf34 is an ER-resident type I transmembrane protein, and might play a role in ER functions including Ca2+ homeostasis and ER stress.


Assuntos
Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Proteínas/metabolismo , Sequência de Aminoácidos , Animais , Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células HEK293 , Células HeLa , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Transporte Proteico/efeitos dos fármacos , Proteínas/química , Proteínas/genética , Tunicamicina/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-24524591

RESUMO

OBJECTIVES: To assess the effectiveness of a comprehensive workplace stress management program consisting of participatory action-oriented training (PAOT) and individual management. METHODS: A comprehensive workplace stress management program was conducted in a medium-sized enterprise. The baseline survey was conducted in September 2011, using the Korean Occupational Stress Scale (KOSS) and Worker's Stress Response Inventory (WSRI). After implementing both organizational and individual level interventions, the follow up evaluation was conducted in November 2011. RESULTS: Most of the workers participated in the organizational level PAOT and made Team-based improvement plans. Based on the stress survey, 24 workers were interviewed by a researcher. After the organizational and individual level interventions, there was a reduction of several adverse psychosocial factors and stress responses. In the case of blue-collar workers, psychosocial factors such as the physical environment, job demands, organizational system, lack of rewards, and occupational climate were significantly improved; in the case of white-collar workers, the occupational climate was improved. CONCLUSIONS: In light of these results, we concluded that the comprehensive stress management program was effective in reducing work-related stress in a short-term period. A persistent long-term follow up is necessary to determine whether the observed effects are maintained over time. Both team-based improvement activities and individual interviews have to be sustainable and complementary to each other under the long-term plan.

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