ABSTRACT
Background@#Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels. @*Methods@#We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays. @*Results@#During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function. @*Conclusion@#Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.
ABSTRACT
Objective@#Despite the rapid increase in problematic media device use, relatively little is known about specific characteristics and extent of problematic media device and how they relate to different psychological features. @*Methods@#Data extracted from the Panel Korea Study for the Child Cohort Study were used. At the age of 9 years, media device addiction severity was assessed using the K-scale, and children’s behavioral outcomes were assessed using the Child Behavior Checklist. Among children with problematic media device use (n=339), we performed latent profile analysis using the K-scale to identify subtypes of problematic media device use, and then compared the child behavioral problems and executive function according to the different subtypes of problematic media device use. @*Results@#Children with problematic media device use were divided into class 1 (n=51), class 2 (n=138), and class 3 (n=150). Compared with classes 2 and 3, class 1 had more severe problematic media device use, including daily activity disturbance, withdrawal, and tolerance. Class 1 had the most serious behavioral problems and executive function difficulties among classes. Class 2 had greater daily activity disturbance and tolerance than those of class 3, but executive function showed no significant difference between the two classes. In logistic regression analysis, behavioral problems except for somatization were more common in class 1 than in the control group. @*Conclusion@#Results suggest that problematic media device use is associated with significant behavioral problem and executive function difficulties and underscore the need for further clinical and research attention for these specific subgroup members.
ABSTRACT
Background@#High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. @*Methods@#Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. @*Results@#AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. @*Conclusion@#These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.
ABSTRACT
Objective@#Despite the rapid increase in problematic media device use, relatively little is known about specific characteristics and extent of problematic media device and how they relate to different psychological features. @*Methods@#Data extracted from the Panel Korea Study for the Child Cohort Study were used. At the age of 9 years, media device addiction severity was assessed using the K-scale, and children’s behavioral outcomes were assessed using the Child Behavior Checklist. Among children with problematic media device use (n=339), we performed latent profile analysis using the K-scale to identify subtypes of problematic media device use, and then compared the child behavioral problems and executive function according to the different subtypes of problematic media device use. @*Results@#Children with problematic media device use were divided into class 1 (n=51), class 2 (n=138), and class 3 (n=150). Compared with classes 2 and 3, class 1 had more severe problematic media device use, including daily activity disturbance, withdrawal, and tolerance. Class 1 had the most serious behavioral problems and executive function difficulties among classes. Class 2 had greater daily activity disturbance and tolerance than those of class 3, but executive function showed no significant difference between the two classes. In logistic regression analysis, behavioral problems except for somatization were more common in class 1 than in the control group. @*Conclusion@#Results suggest that problematic media device use is associated with significant behavioral problem and executive function difficulties and underscore the need for further clinical and research attention for these specific subgroup members.
ABSTRACT
Background@#High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. @*Methods@#Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. @*Results@#AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. @*Conclusion@#These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.
ABSTRACT
Objectives@#：This study evaluated the medical communication skills of trainee doctors and analyzed the relationship between medical communication skills, self-efficacy on clinical performance (SECP) and empathy. @*Methods@#：A total of 106 trainee doctors from a university hospital participated. The questionnaire comprised self-evaluated medical communication skills, modified SECP and the Korean version of the Jefferson Scale of Empathy-Health Professionals version. The mean difference in medical communication skills scores according to gender, age, division (intern, internal medicine group or surgery group) and position (intern, first-/second- and third-/fourth-year residents) were analyzed. Pearson correlation coefficients were determined between medical communication skills, modified SECP and empathy. The effects of each variable on medical communication skills were verified using the structural equation model. @*Results@#：There were no statistically significant mean differences in self-evaluated medical communication skills according to gender, age, division or position. Medical communication skills had a significant positive correlation with modified SECP (r=0.782, p<0.001) and empathy (r=0.210, p=0.038). Empathy had a direct effect on modified SECP (β=0.30, p<0.01) and modified SECP had a direct effect on medical communication skills (β=0.80, p<0.001). Empathy indirectly influenced medical communication skills, mediating modified SECP (β=0.26, p<0.05). @*Conclusions@#：Medical communication skills are an important core curriculum of residency programs, as they have a direct correlation with SECP, which is needed for successful treatment. Moreover, the medical communication needs a new understanding that is out of empathy.
ABSTRACT
Background@#Globally, YouTube is one of the most popular websites, and the content is not restricted to entertainment. The purpose of this study was to assess the quality of information in YouTube videos pertaining to hysterectomy. @*Methods@#We explored YouTube using the search terms “hysterectomy” and “remove uterus.” The videos that appeared were sorted using the filter “sort by view count.” Of the initial 100 videos, the top 50 videos for each search term were included for review, as determined by the “relevance” filter based on YouTube's algorithm. After excluding 34 videos for various reasons, 66 were included in the final analysis. Each video rated as “useful” was further analyzed for reliability and completeness of information; a set of pre-determined criteria were modified from a previous study and used to grade the quality of videos. @*Results@#The top 66 videos on hysterectomy had a total of 4,679,118 views. Based on authorship, the videos were categorized as follows: videos uploaded by patients, 37%; academic videos, 35%; videos uploaded by physicians, 13%; commercial videos, 4%; and videos uploaded by non-physicians, 2%. The type of content was also categorized: 50% of the videos recorded personal experiences, 23% recorded surgical techniques, 21% involved explanations of the surgery, and 4% were commercial videos. The majority of the videos made by patients were negatively biased toward hysterectomy surgery (71.72%), while the majority of those made by academics or physicians were surgical educational videos for doctors, not patients. @*Conclusion@#YouTube is currently not an appropriate source for patients to gain information on hysterectomy. Physicians should be aware of the limitations and provide up-to-date and peer-reviewed content on the website.
ABSTRACT
Subject(s)
Humans , Adenosine Triphosphate , Dialysis , Luciferases , Peritoneal Dialysis , Prospective Studies , Receptors, Aryl Hydrocarbon , Renal Dialysis , Renal Insufficiency, Chronic , Risk Factors , UremiaABSTRACT
Purpose@#This study examined the effects of action observational training to improve the gait function for patients with stroke. @*Methods@#The participants were divided into two groups: right hemiplegia group (n=12) and left hemiplegia group (n=12). All groups received conventional therapy for five sessions for 30 minutes, each for three weeks. Left and right hemiplegia group practiced additional action observational training for five sessions for 20 minutes each for three weeks. They participated in three weeks of action observational training coupled with immediate physical practice (intervention), followed by a final assessment. The duration of each action observation video sequence was 10 minutes, followed immediately by practice of the observed motor skill (10 minutes). The gait velocity, cadence, swing time, step length, and BOS (base of support) were examined using the GAITRite system. @*Results@#The results of this study showed significant improvement in the gait function. The outcomes of the gait abilities from gait velocity, cadence, swing time, step length of the affected side, and BOS (base of support) were improved significantly in the right hemiplegia group (p<0.05). In the left hemiplegia group, there was no significant improvement in the gait velocity, cadence, and BOS except for the swing time and step length of the affected side. The left and right group comparisons between the groups were not significant (p<0.05). @*Conclusion@#Action observation training improves the gait function. These results suggest that action observational training is feasible and suitable for stroke patients.
ABSTRACT
Purpose@#This study examined the effects of action observational training to improve the gait function for patients with stroke. @*Methods@#The participants were divided into two groups: right hemiplegia group (n=12) and left hemiplegia group (n=12). All groups received conventional therapy for five sessions for 30 minutes, each for three weeks. Left and right hemiplegia group practiced additional action observational training for five sessions for 20 minutes each for three weeks. They participated in three weeks of action observational training coupled with immediate physical practice (intervention), followed by a final assessment. The duration of each action observation video sequence was 10 minutes, followed immediately by practice of the observed motor skill (10 minutes). The gait velocity, cadence, swing time, step length, and BOS (base of support) were examined using the GAITRite system. @*Results@#The results of this study showed significant improvement in the gait function. The outcomes of the gait abilities from gait velocity, cadence, swing time, step length of the affected side, and BOS (base of support) were improved significantly in the right hemiplegia group (p<0.05). In the left hemiplegia group, there was no significant improvement in the gait velocity, cadence, and BOS except for the swing time and step length of the affected side. The left and right group comparisons between the groups were not significant (p<0.05). @*Conclusion@#Action observation training improves the gait function. These results suggest that action observational training is feasible and suitable for stroke patients.
ABSTRACT
PURPOSE: This study examined the effects of horse riding simulator exercise on the thickness changes in the transverse abdominis in normal adults. METHODS: Forty-five healthy adults were recruited and randomized to a horseback riding simulation exercise group (n=15), a sling exercise group (n=15), and a trunk stabilization exercise group (n=15). A horseback riding simulator offers the indoor experience of horseback riding and mimics the rhythmic movement of horseback riding, thereby provided a virtual environment, such as riding a real horse on the front screen. The velocity of the horse riding simulator exercise was regulated within the subject's ability to control the exercise on the horse riding simulator. A sling exercise group performed sling exercise under the inspection of the experimenter. In the trunk stabilization exercise group, the subjects were instructed to perform the exercise accurately and pause the session when pain occurred during the intervention. The subjects in each group carried out the interventions three times per week for six weeks. The thickness of the transverse abdominis was measured using a pressure biofeedback unit and the ultrasound. RESULTS: Significant differences in the thickness of transverse abdominis within the groups were observed between before and after the interventions. On the other hand, there were no differences in the parameters among the groups. CONCLUSION: Horse riding simulator exercise can be an alternative to trunk stabilization exercise by increasing the thickness of the transverse abdominis in healthy adults.
Subject(s)
Adult , Humans , Biofeedback, Psychology , Hand , Horses , UltrasonographyABSTRACT
Mitochondrial deficits or altered expressions of microRNAs are associated with the pathogenesis of various diseases, and microRNA-operated control of mitochondrial activity has been reported. Using a retrovirus-mediated short-hairpin RNA (shRNA) system, we observed that miR-24-mediated H2AX knockdown (H2AX-KD) impaired both mitochondria and the insulin signaling pathway. The overexpression of miR-24 decreased mitochondrial H2AX and disrupted mitochondrial function, as indicated by the ATP content, membrane potential and oxygen consumption. Similar mitochondrial damage was observed in shH2AX-mediated specific H2AX-KD cells. The H2AX-KD reduced the expression levels of mitochondrial transcription factor A (TFAM) and mitochondrial DNA-dependent transcripts. H2AX-KD mitochondria were swollen, and their cristae were destroyed. H2AX-KD also blocked the import of precursor proteins into mitochondria and the insulin-stimulated phosphorylation of IRS-1 (Y632) and Akt (S473 and T308). The rescue of H2AX, but not the nuclear form of ΔC24-H2AX, restored all features of miR-24- or shH2AX-mediated impairment of mitochondria. Hepatic miR-24 levels were significantly increased in db/db and ob/ob mice. A strong feedback loop may be present among miR-24, H2AX, mitochondria and the insulin signaling pathway. Our findings suggest that H2AX-targeting miR-24 may be a novel negative regulator of mitochondrial function and is implicated in the pathogenesis of insulin resistance.
Subject(s)
Animals , Mice , Adenosine Triphosphate , Insulin Resistance , Insulin , Membrane Potentials , MicroRNAs , Mitochondria , Oxygen Consumption , Phosphorylation , RNA , Transcription FactorsABSTRACT
PURPOSE: The purpose of this study was to describe cleaning workers' working experiences in Korea. METHODS: The data were collected in two focus-group interviews with 9 cleaning workers. The phenomenological analytic method suggested by Colaizzi was used to analyze the data. RESULTS: Five theme clusters and thirteen themes emerged from the analysis. The first theme clusters, 'Dead-end choice' included Limits of elderly women workers, Financial difficulties, Lowered self-esteem. The second theme clusters, 'Facing with discriminatory working environments' included Fear and unfair working conditions. The third theme clusters, 'Potential health problems' included Physical overload, Repeated exposure to hazardous substances and Emotional labor. The fourth theme clusters, 'Excluded from protection of the law' included Gloomy reality and Sexual harassment. The fifth theme clusters, 'Desire to get out of social isolation' included Efforts to maintain the status, Desire to live confidently and Desire to change social recognition. CONCLUSION: The findings of the study provide understanding on cleaning workers' working experiences to explain by their vision and language and should ensure proper working conditions and environment to live a better life.
Subject(s)
Aged , Female , Humans , Focus Groups , Hazardous Substances , Interviews as Topic , Korea , Occupational Health Nursing , Qualitative Research , Sexual Harassment , Women, WorkingABSTRACT
Low density lipoprotein receptor (LDLR) plays an important role in the cholesterol homeostasis. We examined the possible circadian regulation of LDLR and mechanism(s) underlying it. In mice, blood glucose and plasma triglyceride, total and high density lipoprotein cholesterol varied distinctively throughout a day. In addition, LDLR mRNA oscillated in the liver in a functional clock-dependent manner. Accordingly, analysis of human LDLR promoter sequence revealed three putative E-boxes, raising the possible regulation of LDLR expression by E-box-binding transcription factors. To test this possibility, human LDLR promoter reporter constructs were transfected into HepG2 cells and the effects of CLOCK/BMAL1, Hes1, and Hes6 expression were analyzed. It was found that positive circadian transcription factor complex CLOCK/BMAL1 upregulated human LDLR promoter activity in a serum-independent manner, while Hes family members Hes1 and Hes6 downregulated it only under serum-depleted conditions. Both effects were mapped to proximal promoter region of human LDLR, where mutation or deletion of well-known sterol regulatory element (SRE) abolished only the repressive effect of Hes1. Interestingly, hes6 and hes1 mRNA oscillated in an anti-phasic manner in the wild-type but not in the per1-/-per2-/- mouse. Comparative analysis of mouse, rat and human hes6 genes revealed that three E-boxes are conserved among three species. Transfection and site-directed mutagenesis studies with hes6 reporter constructs confirmed that the third E-box in the exon IV is functionally induced by CLOCK/BMAL1. Taken together, these results suggest that LDLR expression is under circadian control involving CLOCK/BMAL1 and Hes family members Hes1 and Hes6.
Subject(s)
Animals , Humans , Male , Mice , ARNTL Transcription Factors/physiology , Base Sequence , Basic Helix-Loop-Helix Transcription Factors/genetics , CLOCK Proteins/physiology , Cholesterol/blood , Circadian Rhythm , E-Box Elements , Exons , Gene Expression Regulation , Hep G2 Cells , Homeodomain Proteins/genetics , Homeostasis , Liver/metabolism , Mice, Inbred C57BL , Promoter Regions, Genetic , Receptors, LDL/genetics , Repressor Proteins/genetics , Transcription, GeneticABSTRACT
Cholesterol 7alpha-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin-Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.
Subject(s)
Animals , Humans , Mice , Rats , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics , Forkhead Transcription Factors/genetics , Gene Expression Regulation/drug effects , Glucose/metabolism , Hep G2 Cells , Insulin/pharmacology , Lipid Metabolism/drug effects , Liver/metabolism , Mice, Inbred C57BL , Mutagenesis, Site-Directed , Nerve Tissue Proteins/genetics , Protein Binding/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Sequence Deletion/genetics , Signal Transduction/drug effects , Transcriptional Activation/drug effectsABSTRACT
Cholesterol 7alpha-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin-Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.
Subject(s)
Animals , Humans , Mice , Rats , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics , Forkhead Transcription Factors/genetics , Gene Expression Regulation/drug effects , Glucose/metabolism , Hep G2 Cells , Insulin/pharmacology , Lipid Metabolism/drug effects , Liver/metabolism , Mice, Inbred C57BL , Mutagenesis, Site-Directed , Nerve Tissue Proteins/genetics , Protein Binding/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Sequence Deletion/genetics , Signal Transduction/drug effects , Transcriptional Activation/drug effectsABSTRACT
PURPOSE: This study aimed to identify factors affecting the use of the hearing protection devices (HPDs) among workers exposed to noise using the Pender Health Promotion Model. METHODS: The 222 subjects came from thermal power plants with similar noise levels, which are between 80 dB and 90 dB in South Korea. Data were collected with self-administered questionnaires designed to measure concepts from the Health Promotion Model. RESULTS: Mean percent times of using the HPDs at their most recent job site were 50.9%, and 20.3% had never the HPDs. The predictors of HPD use were social modeling (OR = 1.380), perceived benefits (OR = 1.150), and working at noisy worksites (OR = 4.925) when the outcome was based on the "non-use" versus "used at least once". However, the predictors of HPD use were social modeling (OR = 1.795) and perceived benefits (OR = 1.139) based on the "less than half-of-the-time-use" versus "more than half-of-the-time-use". CONCLUSION: Social modeling and perceived benefits of using the HPDs are important for workers to keep minimal or certain level of using the HPDs.
Subject(s)
Ear Protective Devices , Health Promotion , Hearing , Noise , Porphyrins , Power Plants , Republic of Korea , Workplace , Surveys and QuestionnairesABSTRACT
BACKGROUND: The characterization of progenitor/keratinocyte stem cells (KSC) remains an unachieved goal. A previous study showed that rapid adhering cells to collagen IV had the characteristics of putative progenitor/KSCs. OBJECTIVE: The purpose of this study was to investigate the genetic expression of rapid adhering cells compared to non adhering cells to determine the characteristic of KSCs. METHODS: We isolated rapid adhering cells representative of KSCs from non adhering cells representative of transient amplifying cells. In addition, we differentiated cells from human tonsilar keratinocytes utilizing the adhering capability of the KSCs to collagen IV. Annealing control primer based differentially displayed polymerase chain reaction (PCR) was performed as well as Western blot analysis. RESULTS: The levels of mitochondria-related gene expression were low in the rapid adhering cells compared to the non adhering cells. Mitochondrial complex I, COX IV, peroxiredoxins (I, II and IV) and mitochondrial membrane potential were all low in the rapid adhering cells compared to the non adhering cells. CONCLUSION: Using an adhesion method on human collagen IV-coated plates, our results suggest that reduced mitochondrial function may be an important characteristic of KSCs.
Subject(s)
Humans , Blotting, Western , Collagen , Gene Expression , Keratinocytes , Membrane Potential, Mitochondrial , Mitochondria , Peroxiredoxins , Polymerase Chain Reaction , Stem CellsABSTRACT
Peroxisome proliferator activated receptor (PPAR) gamma coactivator-1alpha (PGC-1alpha) may be implicated in cholesterol metabolism since PGC-1alpha co-activates estrogen receptor alpha (ERalpha) transactivity and estrogen/ERalpha induces the transcription of LDL receptor (LDLR). Here, we show that overexpression of PGC-1alpha in HepG2 cells represses the gene expression of LDLR and does not affect the ERalpha-induced LDLR expression. PGC-1alpha suppressed the LDLR promoter-luciferase (pLR1563-luc) activity regardless of cholesterol or functional sterol-regulatory element-1. Serial deletions of the LDLR promoter revealed that the inhibition by PGC-1alpha required the LDLR promoter regions between -650 bp and -974 bp. Phosphorylation of PGC-1alpha may not affect the suppression of LDLR expression because treatment of SB202190, a p38 MAP kinase inhibitor, did not reverse the LDLR down-regulation by PGC-1alpha. This may be the first report showing the repressive function of PGC-1alpha on gene expression. PGC-1alpha might be a novel modulator of LDLR gene expression in a sterol-independent manner, and implicated in atherogenesis.
Subject(s)
Humans , Base Sequence , Cell Line, Tumor , Cholesterol/metabolism , Estrogen Receptor alpha/metabolism , Gene Expression Regulation , Heat-Shock Proteins/genetics , Molecular Sequence Data , Promoter Regions, Genetic , RNA, Messenger/genetics , Receptors, LDL/genetics , Sterol Regulatory Element Binding Protein 2/metabolism , Transcription Factors/genetics , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsABSTRACT
Insulin-like growth factor (IGF)/IGF binding protein (IGFBP) abnormalities may be important in the pathogenesis of growth failure in chronic renal failure (CRF). We induced experimental CRF by 5/6 nephrectomy in Sprague Dawley rats (100 g) and observed for 2 weeks comparing with sham-operated pair-fed control rats (Sham- C). CRF rats gained 30% less height than Sham- C rats (P10 kDa, containing IGFBPs) and low (<10 kDa, containing free IGF) molecular weight fractions using a gel filtration column. Both fractions obtained from CRF sera decreased the growth of control chondrocytes up to 40% compared with those from control sera. We suggest that the pathogenesis of growth failure in CRF may be involved in the increase of circulating IGFBP4 as well as the unidentified small molecular weight uremic serum factors which block the growth of chondrocytes in growth plate.