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1.
Anat Sci Educ ; 17(4): 796-805, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38487974

ABSTRACT

It can be difficult for some students to learn three-dimensional anatomical structure concepts. While virtual reality (VR) systems have been reported as helpful for learning, there has been scarce research on either VR teaching strategies or the influence of visually induced motion sickness (VIMS) in the context of large anatomy classes (i.e., over 100 students). The study thus aimed to (1) establish a VR anatomy instruction video for a large class; (2) determine how many students experience VIMS when watching a VR anatomy instruction video; (3) evaluate the influence of VIMS on VR anatomy video-based learning; and (4) examine whether a small screen size alleviates VIMS. Laboratory course students viewing a VR anatomy instruction video about the vascular system were invited to participate in the questionnaire survey. Anatomy faculty and staff participated in an experimental trial to determine whether small screen size could alleviate VIMS. The Likert scale survey revealed that students reported the VR strategy as advantageous and appropriate for large classes, but that it cannot replace practical dissection. Of the total participants, 32% reported experiencing VIMS, and 40% of those experiencing VIMS agreed that this could negatively impact their learning through a VR anatomy instruction video. Adjusting the screen size from large to small significantly delayed the onset of VIMS. In conclusion, the VR anatomy instruction video strategy is feasible and helpful for large classes, but educators should consider VIMS when planning their use of this teaching approach.


Subject(s)
Anatomy , Education, Medical, Undergraduate , Students, Medical , Virtual Reality , Humans , Anatomy/education , Pilot Projects , Students, Medical/psychology , Students, Medical/statistics & numerical data , Female , Male , Education, Medical, Undergraduate/methods , Young Adult , Surveys and Questionnaires , Adult , Learning , Computer-Assisted Instruction/methods , Curriculum
2.
Mol Neurobiol ; 61(2): 707-724, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37656312

ABSTRACT

The role of heat shock protein 27 (HSP27), a chaperone, in neuropathic pain after nerve injury has not been systematically surveyed despite its neuroprotective and regeneration-promoting effects. In this study, we found that HSP27 expression in sensory neurons of the dorsal root ganglia (DRG) mediated nerve injury-induced neuropathic pain. Neuropathic pain behaviors were alleviated by silencing HSP27 in the DRG of a rat spinal nerve ligation (SNL) model. Local injection of an HSP27-overexpression construct into the DRG of naïve rats elicited neuropathic pain behaviors. HSP27 interacted with a purinergic receptor, P2X3, and their expression patterns corroborated the induction and reversal of neuropathic pain according to two lines of evidence: colocalization immunohistochemically and immunoprecipitation biochemically. In a cell model cotransfected with HSP27 and P2X3, the degradation rate of P2X3 was reduced in the presence of HSP27. Such an alteration was mediated by reducing P2X3 ubiquitination in SNL rats and was reversed after silencing HSP27 in the DRGs of SNL rats. In summary, the interaction of HSP27 with P2X3 provides a new mechanism of injury-induced neuropathic pain that could serve as an alternative therapeutic target.


Subject(s)
HSP27 Heat-Shock Proteins , Neuralgia , Animals , Rats , Ganglia, Spinal/metabolism , HSP27 Heat-Shock Proteins/metabolism , Hyperalgesia/metabolism , Neuralgia/metabolism , Rats, Sprague-Dawley , Spinal Nerves/metabolism , Receptors, Purinergic P2X3/metabolism
3.
Eur J Dent Educ ; 27(4): 1077-1087, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36976652

ABSTRACT

INTRODUCTION: Modified teaching strategies (MTS), asynchronous online teaching and smaller dissection groups, were applied to a gross anatomy course for dental students in the National Taiwan University in April 2020 in response to the COVID-19 pandemic. This study aimed to investigate the effects and perceptions of MTS on dental students. MATERIALS AND METHODS: Scores for anatomy examinations for 2018-2019 (without MTS) and 2019-2020 (with MTS) cohorts were compared to explore the effect on academic performance. Moreover, questionnaire from the 2019-2020 cohort was analysed to determine dental students' perceptions about MTS. RESULTS: The lecture performance in the final examination of the second semester for the 2019-2020 cohort was significantly higher than that of the first semester (pre-COVID-19) and that for the 2018-2019 cohort. However, the laboratory performance in the midterm examination of the second semester for the 2019-2020 cohort was significantly lower than that for the 2018-2019 cohort and showed no difference in the final examination of the first semester. The questionnaires revealed that the majority of students displayed positive attitudes towards MTS and agreed with the importance of peer discussion during laboratory dissection. CONCLUSIONS: Asynchronous online learning for anatomy lecture may be beneficial for dental students; however, a smaller dissection group accompanied by reduced peer discussion may temporarily exert negative effects on their laboratory performance at the beginning of the application. Furthermore, more dental students exhibited positive perceptions towards smaller dissection groups. These findings could illuminate the learning condition of dental students in anatomy education.


Subject(s)
Academic Performance , Anatomy , COVID-19 , Education, Medical, Undergraduate , Students, Medical , Humans , Learning , Students, Dental , Pandemics , Education, Dental , Anatomy/education , Teaching , Curriculum
4.
BMC Med Educ ; 22(1): 341, 2022 May 04.
Article in English | MEDLINE | ID: mdl-35505291

ABSTRACT

BACKGROUND: Registered nurses are required for high-quality healthcare. Thus, the anatomy course is essential regarding professional knowledge of the human body during the nursing training process. However, previous studies have indicated that anatomy teaching time and anatomy teachers were reduced and insufficient. Therefore, to improve the learning of practical anatomy in response to these difficulties, a bilingual National Taiwan University web-based anatomy atlas (NTU-WAA) was created as a cross-platform application and its feasibility was evaluated. METHODS: The comparison of anatomy examination scores between nursing students of two cohorts (66 from the 2018-2019 cohort, whom was without NTU-WAA application; 54 from the 2019-2020 cohort, to whom NTU-WAA was offered) and the evaluation of questionnaires collected from nursing students of the 2019-2020 cohort and 4 anatomy teachers were carried out to define the feasibility of this strategy. RESULTS: Results obtained by nursing students for the 2019-2020 cohort showed a significant increase in anatomy learning performance compared with that of the 2018-2019 cohort with reference to the laboratory midterm [2018-2019 cohort vs. 2019-2020 cohort, mean (standard deviation, SD): 77.20 (16.14) vs. 81.80 (12.03); p = 0.043], the laboratory final examination [59.68 (15.28) vs. 80.35 (13.74); p < 0.001] and the theory final examination [80.85 (10.10) vs. 84.33 (6.925); p = 0.017]. Moreover, results of the questionnaires indicated that the new bilingual cross-platform atlas was highly accepted by students and teachers. CONCLUSIONS: The NTU-WAA, a bilingual web-based atlas, was evaluated as a beneficial anatomy-learning tool that may enhance self-study of nursing students with consequent amelioration of their anatomy-related performance in both theoretical and laboratory examinations. This reflection suggests the future implementation of the bilingual web-based atlas on a large scale.


Subject(s)
Students, Nursing , Educational Measurement/methods , Humans , Internet , Learning , Surveys and Questionnaires
5.
Anat Sci Educ ; 15(3): 476-492, 2022 May.
Article in English | MEDLINE | ID: mdl-35291048

ABSTRACT

Due to the Covid-19 pandemic, National Taiwan University anatomy teachers adopted asynchronous online video teaching and reduced the size of anatomy laboratory groups in April 2020. The aim of this study was to investigate the impact of these changes on medical students' learning. Before Covid-19, the performance of the 2019-2020 cohort was significantly better than that of the 2018-2019 cohort. However, the implementation of modified teaching strategies significantly lowered the laboratory midterm score of the 2019-2020 cohort in the second semester. Conversely, the final laboratory examination score of the 2019-2020 cohort was significantly higher than that of the 2018-2019 cohort. Through correlation analysis, lecture and laboratory examination scores were highly correlated. Additionally, the difference in lecture and laboratory z-scores between two cohorts, the Likert scale survey and free-text feedback of the 2019-2020 cohort, were conducted to show the impact of modified teaching strategies. There were several important findings in this study. First, the change in teaching strategies may temporarily negatively influence medical students to learn anatomy. Besides, analyzing the performance of laboratory assessments could be a complementary strategy to evaluate online assessments. Applying lecture examination scores to predict laboratory performance was a feasible way to identify students who may have difficulty in learning practical dissection. Finally, reducing group size together with reduced peer discussion may have a negative effect on learning cadaver dissection for students with low academic performance. These findings should be taken into consideration when anatomy teachers apply new teaching strategies in anatomy courses.


Subject(s)
Anatomy , COVID-19 , Students, Medical , Anatomy/education , Cadaver , Educational Measurement , Humans , Pandemics , Teaching
6.
Ann Neurol ; 91(6): 821-833, 2022 06.
Article in English | MEDLINE | ID: mdl-35285061

ABSTRACT

OBJECTIVE: Although the microenvironment for peripheral nerve regeneration is permissive, such a mechanism is defective in diabetes, and the molecular mediators remain elusive. [Correction added on May 11, 2022, after first online publication: In the preceding sentence, "is ok" was changed to "is defective".] This study aimed to (1) investigate the relationship between skin innervation and collagen pathology in diabetic neuropathy and to (2) clarify the molecular alterations that occur in response to hyperglycemia and their effects on axon regeneration. METHODS: We addressed this issue using two complementary systems: (1) human skin from patients with diabetic neuropathy and to (2) a coculture model of human dermal fibroblasts (HDFs) with rat dorsal root ganglia neurons in the context of intrinsic neuronal factor and extrinsic microenvironmental collagen and its biosynthetic pathways. RESULTS: In diabetic neuropathy, the skin innervation of intraepidermal nerve fiber density (IENFd), a measure of sensory nerve degeneration, was reduced with similar expression of a growth associated protein 43, a marker of nerve regeneration. In contrast, the content and packing of collagen in the diabetic skin became more rigid than the control skin. Sec31a, a protein that regulates the collagen biosynthetic pathway, was upregulated and inversely correlated with IENFd. In the cell model, activated HDFs exposed to high-glucose medium enhanced the expression of Sec31a and collagen I through the activation of transforming growth factor ß, a profibrotic molecule. Sec31a upregulation impaired neurite outgrowth. This effect was reversed by silencing Sec31a expression and neurite outgrowth was resumed. INTERPRETATION: The current study provides evidence that Sec31a plays a key role in inhibiting nerve regeneration in diabetic neuropathy. ANN NEUROL 2022;91:821-833.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Neuropathies , Animals , Axons/pathology , Diabetes Mellitus, Experimental/pathology , Diabetic Neuropathies/pathology , Ganglia, Spinal/pathology , Humans , Nerve Regeneration , Rats , Skin/pathology
7.
J Epidemiol ; 31(9): 503-510, 2021 09 05.
Article in English | MEDLINE | ID: mdl-32741854

ABSTRACT

BACKGROUND: To investigate all-cause and cause-specific mortality in Taiwanese patients with type 1 diabetes. METHODS: A cohort of 17,203 patients with type 1 diabetes were identified from Taiwan's National Health Insurance claims in the period of 1998-2014. Person-years were accumulated for each individual from date of type 1 diabetes registration to date of death or the last day of 2014. Age, sex, and calendar year standardized mortality ratios (SMRs) were calculated with reference to the general population. RESULTS: In up to 17 years of follow-up, 4,916 patients died from 182,523 person-years. Diabetes (30.15%), cancer (20.48%), circulatory diseases (13.14%), and renal diseases (11.45%) were the leading underlying causes of death. Mortality rate (26.93 per 1,000 person-years) from type 1 diabetes in Taiwan was high, the cause of death with the highest mortality rate was diabetes (8.12 per 1,000 person-years), followed by cancer (5.52 per 1,000 person-years), and circulatory diseases (3.54 per 1,000 person-years). The all-cause SMR was significantly elevated at 4.16 (95% confidence interval, 4.04-4.28), with a greater all-cause SMR noted in females than in males (4.62 vs 3.79). The cause-specific SMR was highly elevated for diabetes (SMR, 16.45), followed by renal disease (SMR, 14.48), chronic hepatitis and liver cirrhosis (SMR, 4.91) and infection (SMR, 4.59). All-cause SMRs were also significantly increased for all ages, with the greatest figure noted for 15-24 years (SMR, 8.46). CONCLUSIONS: Type 1 diabetes in both genders and all ages was associated with significantly elevated SMRs for all-cause and mostly for diabetes per se and renal disease.


Subject(s)
Diabetes Mellitus, Type 1/mortality , Adolescent , Adult , Cause of Death/trends , Child , Child, Preschool , Cohort Studies , Diabetes Mellitus, Type 1/therapy , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mortality/trends , Taiwan/epidemiology , Young Adult
8.
J Diabetes ; 9(6): 622-627, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27485041

ABSTRACT

BACKGROUND: Population-based data for diabetic hand syndrome (DHS) are limited. The aim of the present epidemiological study was to estimate the overall and cause-specific prevalence and rate ratio (RR) of DHS in patients with diabetes. METHODS: The present study was a cross-sectional study based on a random sample of 57 093 diabetics and matched controls, both identified from Taiwan National Health Insurance claims in 2010. The DHS analyzed in the present study included carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint mobility (LJM), and Dupuytren's disease (DD). RESULTS: The prevalence of overall DHS was estimated at 2472 per 105 for the diabetics, compared with 1641 per 105 for the controls, representing a prevalence RR of 1.51 (95 % confidence interval [CI] 1.39-1.64). Stratified analyses further revealed that the significantly increased prevalence of overall DHS was more evident in females than males (1.59 vs 1.36) and was only noted in diabetics aged ≥35 years. Cause-specific analysis suggested that patients with diabetes had the highest prevalence of CTS (1244 per 105 ), followed by SFT (1209 per 105 ), LJM (39 per 105 ), and DD (6 per 105 ). In addition, diabetes was only significantly associated with CTS (RR 1.34; 95 % CI 1.20-1.51) and SFT (1.74; 95 % CI 1.54-1.97). CONCLUSION: The prevalence of overall and certain cause-specific DHS was significantly elevated in patients with diabetes in Taiwan.


Subject(s)
Carpal Tunnel Syndrome/epidemiology , Diabetes Mellitus/epidemiology , Dupuytren Contracture/epidemiology , Tendon Entrapment/epidemiology , Adult , Age Factors , Aged , Comorbidity , Cross-Sectional Studies , Female , Geography , Humans , Male , Middle Aged , Population Surveillance/methods , Prevalence , Risk Factors , Sex Factors , Taiwan/epidemiology
9.
Sci Rep ; 6: 35612, 2016 10 17.
Article in English | MEDLINE | ID: mdl-27748450

ABSTRACT

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection.


Subject(s)
Ganglia, Spinal/metabolism , Gene Expression , Genetic Vectors/administration & dosage , Green Fluorescent Proteins/metabolism , Injections, Spinal/methods , Animals , Gene Transfer Techniques , Green Fluorescent Proteins/genetics , Plasmids/administration & dosage , Polyethyleneimine , Rats , Rats, Sprague-Dawley , Spinal Nerves
10.
Asian Nurs Res (Korean Soc Nurs Sci) ; 10(4): 289-294, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28057316

ABSTRACT

PURPOSE: The purpose of this study was to understand the situation of diabetes patients receiving examinations for diabetes complications and to explore the factors influencing their intention to receive examinations for diabetes complications. METHODS: A cross-sectional study was performed that included 251 diabetes patients who visited outpatient clinics in Southern Taiwan. A survey using a self-administered questionnaire was conducted from October 2015 to January 2016. The questionnaire included items on demographic characteristics, perceived susceptibility to diabetes complications, perceived seriousness of diabetes complications, perceived benefits of taking action to receive diabetes complication examinations, perceived barriers to taking action to receive diabetes complication examinations, and the intention to receive diabetes complication examinations. The data were analyzed using regression analysis. RESULTS: The percentage of participants who received fundus, foot, and kidney examinations was 67.7%, 61.4%, and 73.3%, respectively. Every point increase on the perceived barriers to taking action to receive diabetes complication examinations scale increased the intention to receive a foot examination in the following year by 0.91 times (p=.002), and every point increase on the perceived susceptibility to diabetes complications scale increased the intention to receive a kidney examination in the following year by 1.19 times (p=.045). CONCLUSIONS: Nurses should shoulder the responsibility to increase patients' intention to receive examination of diabetes complications. The results of this study can be used to promote nurses' care efficacy in preventing diabetes complications. They can also provide medical institutions with information to establish prevention and control policies for diabetes complications.


Subject(s)
Diabetic Angiopathies/prevention & control , Diabetic Nephropathies/prevention & control , Patient Acceptance of Health Care/psychology , Physical Examination/psychology , Ambulatory Care/statistics & numerical data , Cross-Sectional Studies , Diabetic Angiopathies/nursing , Diabetic Angiopathies/psychology , Diabetic Nephropathies/nursing , Diabetic Nephropathies/psychology , Disease Susceptibility/psychology , Early Diagnosis , Female , Humans , Intention , Kidney Function Tests , Male , Middle Aged , Nurse-Patient Relations , Ophthalmoscopy , Perception , Physical Examination/nursing , Physical Examination/statistics & numerical data , Taiwan
11.
J Occup Health ; 53(2): 130-6, 2011.
Article in English | MEDLINE | ID: mdl-21325778

ABSTRACT

OBJECTIVE: To compare occupational exposure to extremely-low-frequency magnetic field (ELF-MF) between dentists practicing in dental clinics and those employed in hospitals. METHODS: Thirty-two dentists who worked at clinics (n=15) and 33 dentists employed at hospital dental departments (n=7) voluntarily provided their informed consent to participate in this measurement study. The study dentists were requested to wear an ELF-MF dosimeter for some 3 h at work to determine their personal exposure. Spot measurements taken at a number of locations in each dental office were used to indicate the work environment exposure level. Additionally, ELF-MF emitted from common dental equipment was also measured. All measurements were performed with EMDEX Lite meters. RESULTS: The average environmental exposure to ELF-MF is higher in clinic dental offices than in hospital dental departments (0.55 vs. 0.15 µT, p=0.008). Personal dosimetry showed that on average, clinic dentists spent 35.71 and 19.39% of their time at exposures above 0.3 and 0.4 µT at work, respectively. The corresponding figures for hospital dentists were 19.61 and 13.92%. Additionally, ELF-MF was greater than 0.4 µT at 30 cm from all selected equipment, but the ELF-MF generally diminished as the distance from dental equipment increased. Uultraviolet air sterilization system produced 3 times as much ELF-MF as other dental equipment. CONCLUSIONS: This study suggests the possibility of over-exposure of dentists to power frequency ELF-MF. Additionally, certain dental equipment may produce ELF-MF levels greater than 0.4 µT in areas where dentists usually work when treating patients.


Subject(s)
Dental Clinics , Dentists , Electromagnetic Fields , Hospitals , Occupational Exposure/analysis , Humans
12.
J Neuropathol Exp Neurol ; 68(12): 1269-81, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19915488

ABSTRACT

We assessed the effects of treatment with 4-methylcatechol (4MC), a known inducer of nerve growth factor, on peripheral nerve regeneration by analyzing cutaneous and muscular reinnervation in mice after sciatic nerve crush injury. At 3 months postinjury, the skin innervation index was significantly higher in the 4MC group than the control group (p=0.0002); there was also increased unmyelinated fiber density (p=0.0042) and unmyelinated fibers/Remak bundle (p = 0.001) in sural nerves, indicating unmyelinated nerve fiber regeneration. These changes were accompanied by increases of transcripts for nerve growth factor (p = 0.0026) and glial cell line-derived neurotrophic factor (p=0.03) in the 4MC group. In contrast, muscle innervation indices were similar in both groups and were higher than the skin innervation index (p < 0.0001). The regeneration of myelinated nerve fibers, as assessed by fiber density, diameter and g ratio analyses in sural nerves, and amplitudes of muscle action potential in sciatic nerves, was similar in both groups. Taken together, these data suggest that 4MC specifically promoted the regeneration of unmyelinated nerve fibers and reinnervation of the skin by increasing the expression of nerve growth factor and glial cell line-derived neurotrophic factor.


Subject(s)
Catechols/pharmacology , Muscle, Skeletal/innervation , Nerve Regeneration/drug effects , Neuroprotective Agents/pharmacology , Skin/innervation , Action Potentials/drug effects , Animals , Gene Expression/drug effects , Immunohistochemistry , Male , Mice , Mice, Inbred ICR , Microscopy, Electron, Transmission , Muscle, Skeletal/drug effects , Nerve Crush , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/ultrastructure , Nerve Fibers, Unmyelinated/drug effects , Nerve Fibers, Unmyelinated/ultrastructure , Nerve Growth Factor/biosynthesis , Nerve Growth Factor/drug effects , Neural Conduction , Neuromuscular Junction/drug effects , Neuromuscular Junction/ultrastructure , Reverse Transcriptase Polymerase Chain Reaction , Sciatic Nerve/injuries , Skin/drug effects
13.
J Proteome Res ; 8(2): 1004-13, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19099420

ABSTRACT

Liver is unique in its capability to regenerate after an injury. Liver regeneration after a 2/3 partial hepatectomy served as a classical model and is adopted frequently to study the mechanism of liver regeneration. In the present study, semiquantitative analysis of protein expression in mouse liver regeneration following partial hepatectomy was performed using an iTRAQ technique. Proteins from pre-PHx control livers and livers regenerating for 24, 48 and 72 h were extracted and inspected using 4-plex isotope labeling, followed by liquid chromatography fractionation, mass spectrometry and statistical differential analysis. A total of 827 proteins were identified in this study. There were 270 proteins for which quantitative information was available at all the time points in both biologically duplicate experiments. Among the 270 proteins, Car3, Mif, Adh1, Lactb2, Fabp5, Es31, Acaa1b and LOC100044783 were consistently down-regulated, and Mat1a, Dnpep, Pabpc1, Apoa4, Oat, Hpx, Hp and Mt1 were up-regulated by a factor of at least 1.5 from that of the controls at one time point or more. The regulation of each differential protein was also demonstrated by monitoring its time-dependent expression changes during the regenerating process. We believe this is the first report to profile the protein changes in liver regeneration utilizing the iTRAQ proteomic technique.


Subject(s)
Hepatectomy , Isotope Labeling/methods , Liver Regeneration/physiology , Liver/chemistry , Protein Array Analysis , Proteins/analysis , Animals , Female , Liver/metabolism , Liver Extracts/chemistry , Mass Spectrometry/methods , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Protein Array Analysis/instrumentation , Protein Array Analysis/methods , Proteome/analysis , Reproducibility of Results
14.
FEBS Lett ; 579(20): 4337-43, 2005 Aug 15.
Article in English | MEDLINE | ID: mdl-16061232

ABSTRACT

This study focused on identifying the signalling mediating the effect of magnolol on corticosterone production. Magnolol-induced corticosterone production was completely inhibited by mitogen-activated protein kinase kinase (MEK)-inhibitor PD98059, tyrosine kinase (TK)-inhibitor genistein or Janus tyrosine kinase 2 (JAK2)-inhibitor AG490, suggesting that extracellular signal-regulated kinase (ERK) and JAK2 are both involved in this signaling cascade. Further, magnolol induced the transient phosphorylation of MEK, ERK, cAMP response-element binding protein (CREB) and the expression of 32 and 30 kDa steroidogenic acute regulatory protein (StAR) in a time-dependent manner. Inhibition of TK or JAK2 activities blocked magnolol-induced phosphorylation of MEK and ERK, again supporting the upstream role of JAK2. The activation of JAK2 or MEK apparently mediated the magnolol-induced phosphorylation of CREB and the upregulation of StAR. These findings demonstrate a novel pathway for magnolol to induce the expression of StAR, which regulates the rate-limiting step in sterodiogenesis.


Subject(s)
Adrenal Cortex/metabolism , Biphenyl Compounds/pharmacology , Corticosterone/biosynthesis , Lignans/pharmacology , Phosphoproteins/metabolism , Signal Transduction , Adrenal Cortex/drug effects , Animals , Cyclic AMP Response Element-Binding Protein/metabolism , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Janus Kinase 2 , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , Rats , Rats, Wistar
15.
Histochem Cell Biol ; 123(4-5): 429-39, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15844002

ABSTRACT

Magnolol stimulates adrenal steroidogenesis and induces the distributional changes of p160 and adipose differentiation-related protein (ADRP) in rat adrenal cells. This study investigated the underlying signaling mechanisms involved in these processes. Magnolol (30 microM) caused a time-dependent increase in the phosphorylation of extracellular signal-related kinase (ERK) in cultured adrenal cells. The following evidence supports a link between ERK activation and p160 translocation. First, the magnolol-induced redistribution of p160 from the lipid droplet surface to the cytosol, resulting in the decrease in the percentages of p160-positive cells, and this decrease in p160-positive cells was completely blocked by pretreatment with either of the MAPK-ERK kinase (MEK) inhibitors PD98059 or U0126. Second, magnolol did not significantly decrease total p160 protein levels but caused an increase in threonine phosphorylation of p160, which reached a maximum after 5 min of magnolol treatment, and this magnolol-induced phosphorylation of p160 was prevented by pretreatment with U0126, suggesting the involvement of ERK. In addition, magnolol decreased both ADRP immunostaining intensity at the lipid droplet surface and the percentage of ADRP-positive cells. This was further confirmed biochemically by the decrease in ADRP levels in total cell homogenates and in lipid droplet fractions. Magnolol-induced decrease in ADRP staining at the lipid droplet surface was not affected by pretreatment with PD98059 or U0126, indicating that ERK signaling was not involved in this event. Furthermore, treatment with 30 microM magnolol for 6 h resulted in about 50% decrease in ADRP protein level. Therefore, decreased protein levels of p160 and ADRP at the lipid droplet surface induced by magnolol were mediated via two different mechanisms: phosphorylation of p160 and downregulation of ADRP expression, respectively.


Subject(s)
Adrenal Glands/drug effects , Biphenyl Compounds/pharmacology , Lignans/pharmacology , Membrane Proteins/metabolism , Transcription Factors/metabolism , Adrenal Glands/cytology , Adrenal Glands/metabolism , Animals , Blotting, Western , Butadienes/pharmacology , Cells, Cultured , Cytoplasmic Granules/metabolism , Enzyme Inhibitors/pharmacology , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Flavonoids/pharmacology , Fluorescent Antibody Technique , Histone Acetyltransferases , Lipid Metabolism , Marine Toxins , Microscopy, Fluorescence , Nitriles/pharmacology , Nuclear Receptor Coactivator 1 , Oxazoles/pharmacology , Perilipin-2 , Phosphoprotein Phosphatases/antagonists & inhibitors , Phosphorylation/drug effects , Protein Transport/drug effects , Pyrans/pharmacology , Rats , Rats, Wistar , Spiro Compounds/pharmacology , Time Factors
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