Circadian Expression of Cryptochrome in Rat Brain and Muscle

Kang, Hae Mook 청주대학교 산업과학연구소 2006 産業科學硏究 Vol.23 No.2

포유류의 일주기 조절에는 두 종류의 cryptochrome(Cry1과 Cry2)이 관여하는 것으로 알려져 있다. 흰쥐에서 Cry1과 Cry2 유전자의 일주기적인 발현을 suprachiasmatic nucleus(SCN)조직과 근육 조직에서 real-time PCR로 조사하였다. SCN 조직에서 Cry1과 Cry2의 발현 정도는 밤낮의 변화에 따른 일주기적인 리듬을 보여주고 있다. 근육 조직 또한 SCN과는 약간 다르지만 분명하게 Cry1과 Cry2의 일주기적인 발현을 하고 있다. 따라서 이 결과는 Cry1과 Cry2가 SCN 조직에서 중추적인 생체시계와 근육조직에서 말단 생체시계의 역할을 하고 있음을 강력히 시사하고 있다. In mammals, two types of cryptochrome (Cry1 and Cry2) are known to involve in the regulation of circadian rhythm. Circadian expression of rat Cry1 and Cry2 mRNA was examined in suprachiasmatic nucleus (SCN) and muscle tissues by real-time PCR. The expression level of Cry1 and Cry2 mRNA in SCN showed circadian rhythm with a peak at the time of day/night transition. Muscle also exhibited the circadian pattern of the expression of Cry1 and Cry2 mRNA at slightly different with that of SCN. It is, therefore, strongly suggested that Cry1 and Cry2 play an important role in central clock of SCN and peripheral clock in muscle.

Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway

Roh, Seung-Eon,Woo, Jung A.,Lakshmana, Madepalli K.,Uhlar, Courtney,Ankala, Vinishaa,Boggess, Taylor,Liu, Tian,Hong, Yun-Hwa,Mook-Jung, Inhee,Kim, Sang Jeong,Kang, David E. The Federation of American Societies for Experimen 2013 The FASEB Journal Vol.27 No.12

<P>Mitochondrial dysfunction and synaptic damage are important features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and tau. We reported previously that the scaffolding protein RanBP9, which is overall increased in brains of patients with AD and in mutant APP transgenic mice, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of APP and β1-integrin, respectively. Moreover, RanBP9 induces neurodegeneration <I>in vitro</I> and <I>in vivo</I> and mediates Aβ-induced neurotoxicity. Here we show in primary hippocampal neurons that RanBP9 potentiates Aβ-induced reactive oxygen species (ROS) overproduction, apoptosis, and calcium deregulation. Analyses of calcium-handling measures demonstrate that RanBP9 selectively delays the clearance of cytosolic Ca<SUP>2+</SUP> mediated by the mitochondrial calcium uniporter through a process involving the translocation of cofilin into mitochondria and oxidative mechanisms. Further, RanBP9 retards the anterograde axonal transport of mitochondria in primary neurons and decreases synaptic mitochondrial activity in brain. These data indicate that RanBP9, cofilin, and Aβ mimic and potentiate each other to produce mitochondrial dysfunction, ROS overproduction, and calcium deregulation, which leads to neurodegenerative changes reminiscent of those seen in AD.—Roh. S.-E., Woo, J. A., Lakshmana, M. K., Uhlar, C., Ankala, V., Boggess, T., Liu, T., Hong, Y.-H., Mook-Jung, I., Kim, S. J., Kang, D. E. Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway.</P>

地域開發을 위한 地方公企業의 役割

朴文玉 檀國大學校 地域硏究所 1986 地域硏究 Vol.7 No.-

退溪의 官僚觀

朴文玉 단국대학교 퇴계학연구소 1987 退溪學硏究 Vol.1 No.-

공황발작과 승모판 탈출

민성길,박묵희,이호영 大韓神經精神醫學會 1986 신경정신의학 Vol.25 No.2

Of 72 Korean patients with recurrent spontaneous panic attacks, none had definite mitral valve prolapse(MVP). With a very low prevalence of MVP in the general population of Korea, this finding suggests that panic disorder without MVP is a universal one regardless of ethnic difference and that the two conditions might be dissociated. Furthermore, panic attack might not be the expression of a genetically determined biological defect which also is underlying MVP. However as seen in the case history of patient with MVP who had felt anxiety symptoms with cardiac symptoms caused by MVP, it is still possible that another form of spontaneous panic attack triggered by arrhythmia of MVP exists.

축구 오버헤드 킥 동작의 운동학적 분석

김의환,이요열,김성섭,권문석,김성호 한국운동역학회 2003 한국운동역학회지 Vol.13 No.1

Kim, E-H · Lee , Y-Y · Kim, S-S· Kwon, M-S · Kim, S-H. The kinematical Analysis of the Overhead Kick on Soccer. Korean Journal of Sport Biomechanics. Vol. 13, No. 1,pp. 155-171. The purpose of this study was to analyze the kinematic variables of over head Kick(OHK) in soccer with three dimensional analysis technique and show the kinematic characteristics of it. The 7 subjects were university football player who have been playing football more than 7 years. The OHK was filmed on 16mm video camera(30frame/sec.) kinematic variables were temporal, postures, and COG(center of gravity). The mean values and the standard deviation for each variables were obtained and used as basic factors for examining characteristics of OHK. the results of this analysis were as follows : Temporal variables : The total time elapsed(TE) of OHK was0.94~1.14sec., the 1st phase was 0.35sec., 2nd phase was 0.46sec., and 3rd phase was 0.22sec.. Posture variables : When subjects performed OHK at the impact event, the ankle and knee angle of kicking foot were more extend than supporting foot. but the hip angle of supporting foot were more extend than kicking foot. Moving distance of the center of mass of the both foot : When subject performed OHK at the impact event, the range of distance on mediolateral direction aspect into right · left shoulder line, anteroposterior direction aspect was 20.9±10.5cm, vertical direction aspect was 92.3±19.9cm. Angular velocity : the faster angular velocity of knee · ankle on the kicking foot grew form jump position to landing position, the faster velocity of ball became. C. O. G. variables : When subject performed OHK at the impact event, upper part of the body was getting lower, lower part of the body was getting higher.

APP 대사과정의 Alpha-secretase의 활성을 조절하는 Furin의 역할 규명

황은미,심혜진,묵인희 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.2

Background:The β-amyloid protein, Aβ, which accumulates in the brains of Alzheimer's disease patients, is derived by proteolysis of the amyloid precursor protein (APP). APP can undergo endoproteolytic processing at three sites, one at the amino terminus of the Aβ domain (by β-secretase), one within the Aβ domain (by α-secretase), and one at the carboxyl terminus of the Aβ domain (by γ-secretase) Constitutive and PKC-regulated α-secretase pathways have been reported to secrete sAPPα. In both pathways, we examined mechanisms of furin, which is known to regulate α-secretase activity Methods:Two methods were used to inhibit the activity of furin:overexpression of prodomain of furin and the infection of furin-specific inhibitor α-1-PDX adenovirus in a COS-7 cell. Real-Time PCR was used to determine the level of mRNA of furin in both the APP transgenic mice and age-matched control mice. Results:As a result of inhibiting the activity of furin, the level of sAPPα was significantly decreased regardless of the PKC activity, and the total level of APP did not change as well In a real-time PCR, there was a significant decrease in the mRNA of furin in APP transgenic mice compared to that of control Conclusion:Our results suggest that furin plays an important role in the processing of APP through α-secretase and that the decrease in the level of furin may be closely related to the mechanisms that lead to Alzheimer's disease.

베타 아밀로이드 형성에 관여하는 효소와 그를 응용한 알츠하이머병 치료법 개발 동향

장창환,정민환,묵인희 한국뇌학회 2001 한국뇌학회지 Vol.1 No.1

알츠하이머병(Alzheimer's disease: AD)은 퇴행성 신경질환으로서 80세 이상 노인의 50% 정도가 고통을 받고 있는 병이다. 그 증상으로는 기억력 및 인지기능의 상실이 서서히 진행되어 나타나며 아직 정확한 병인이나 치료법은 알려지지 않고 있는 실정이다. AD의 병리학적 특징으로는 노인반점(senile plaques), 신경섬유덩어리(neurofibrilary tangles), 그리고 신경세포의 손실(neuronal loss)을 대표적으로 들 수 있다 하겠다. 노인반점의 대부분을 차지하고 있는 응집된 베타아밀로이드 단백질은 여러 가지 실험적 증거들에 의하여 AD의 주요 병인으로 생각되어지고 있다. AD는 크게 젊은 나이에 발병하는 유전성 AD(familial AD)와 원인을 알 수 없는 산발성 AD(sporadic AD)로 나눌 수 있다. 유전성 AD의 경우는 presenilin 1(PS1), presenilin 2(PS2) 혹은 아밀로이드 전구단백질(amyloid precursor protein, APP) 유전인자에 돌연변이가 일어났을 경우 100% AD로 발병하게 된다. 산발성 AD의 경우는 아포지단백질 E(apolipoprotein E)나 α-2 macroglobulin에 돌연변이가 일어났을 때 AD로 진전할 확률이 높아지는 위험인자는 밝혀져 있으나 발병의 정확한 원인은 알려진 것이 없다. 특이한 사항은 산발성이나 유전성 AD 모두 베타아밀로이드 단백질의 과다 침착이 공통적으로 일어난다는 것으로 베타아밀로이드의 AD의 병인으로서의 가능성을 시사하고 있다. 본 논문에서는 베타아밀로이드가 형성되어지는 대사경로를 설명하고 그 중 베타아밀로이드 생성에 관여하는 β-, γ-secretases에 관하여 최근의 연구결과들을 중점적으로 설명할 것이다. 또한 베타아밀로이드의 생성을 저해하는 α-secretase의 후보물질들에 관한 설명과 이러한 secretases들의 조절 및 이를 이용한 치매치료법에 관한 최근 동향을 설명하고자 한다. Alzheimer's disease (AD) is one of the most common senile dementia in elderly population. It is an age-related neurodegenerative disorder. Almost 50% of over 80 years old individuals suffer the problems with AD. Memory deficit which is resulted from degenerated neurons followed by synaptic loss is the major symptom of AD. The pathological hallmarks of AD are (1) extracellular deposit of senile plaques, (2) intracellular neurofibrillary tangles and (3) severe neuronal loss in the brain. Senile plaques consist of a central core of insoluble fibrillary amyloid β-protein (Aβ) surrounded by a halo of dystrophic neurites. Most of AD is sporadic form and less than 10% in AD is familial form. The mutations on the gene of amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) have been found on early-onset familial AD (FAD). Apolipoprotein E is known as a risk factor on late-onset sporadic AD (SAD). Since high level of Aβ deposit is appeared in the patient brains of both FAD and SAD, it is considered that Aβ might be the major cause of AD. Because Aβ is generated from a larger precursor protein, designated APP, understanding APP processing is important. APP is processed through at least two different pathways. The α-secretory pathway involves α- and γ-secretases, generating two secreted protein fragments, sAPP αand p3. Alternatively, the secreted fragments sAPPβ and Aβ are generated out of the β-secretory pathway by the actions of β- and γ-secretases. In this review, mechanism of A βgeneration is discussed with focus on three secretases such as α-, β- and γ-secretases. Also, possible therapeutic approaches is discussed based on the information about basic research results of secretases.

SH-SY5Y Human Neuroblastoma Cell에서 에스트로겐의 신경세포 보호효과에 대한 기전

염지현,김희,홍현석,방오영,허균,묵인희 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.1

Apoptosis is one major mechanism underlying neuronal cell death in degenerative diseases in the central nervous system. Previous studies have shown that estrogen has neuroprotective effects in several neuronal cell death model systems. In the present study, we established a staurosporine-induced apoptotic neuronal cell death system with human SH-SY5Y cell line. 17b-estradiol(E2) blocked staurosporine-induced apoptosis of SH-SY5Y cells as revealed by MTT as well as LDH assay. The cells showed typical DNA fragmentation at 4 h and 8 h following staurosporine treatment, which was attenuated by E2 pretreatment. Staurosporine-induced chromatin condensation was also reduced by E2 treatment. Because apoptotic stimuli are known to induce caspase-3 activation and PARP cleavage, we examined whether E2 blocks these processes. E2 markedly attenuated staurosporine-induced casapase-3 activation and PARP cleavage. This study shows that E2 blocks staurosporine-induced apoptosis in SH-SY5Y human neuroblastoma cells, suggesting that E2 is a neuroprotective agent that may be used for the treatment of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

알쯔하이머병 환자 혈청에서의 베타 아밀로이드 단백질에 대한 특이 항체량 측정 : 알쯔하이머병의 생화학적 진단지표 개발 Development of Biomarker for Alzheimer's Disease Diagnosis

소정온,허지연,심혜진,김종원,나덕렬,이필휴,정선주,박문호,주인수,송미숙,김영호,묵인희 대한치매학회 2004 Dementia and Neurocognitive Disorders Vol.3 No.1

Background:Alzheimer's disease (Ad) is a neurodegenerative disorder that is rapidly increasing with the aging society, requiring a need for early diagnosis and prevention. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. AD is characterized by deposition of senile plaques and neurofibrillary tangles in the brain. Aβ peptide in senile plaques seems to play a central role in the neuropathology of AD. Several biochemical markers for AD are available, including reduced Aβ protein, a change in ratio between Aβ40 and 42 and increased level of tau protein in the cerebrospinal fluid (CSF). Methods:This study analyzes anti-Aβ antibody from serums of AD patients using the ELISA. The levels of anti-Aβ antibody from patients with idiopathic Parkinson's disease or stroke and from normal control were compared to that of AD patients. Results:Our results showed a significantly lower anti-Aβ antibody level in AD compared to those with other neurological diseases or control. Conclusions:These data showed that the anti-Aβ antibody level in the serum may be used to diagnose the presence of AD.