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칼슘/칼모듈린-의존성 단백질 키나아제 I 키나아제에 의한 칼슘/칼모듈린-의존성 단백질 키나아제 Ia의 활성화에 따른 효소반응 특성의 변화
조정숙(Jung Sook Cho) 대한약학회 1997 약학회지 Vol.41 No.6
The activity of Ca2+/calmodulin (CaM)-dependent protein kinase Ia (CaM kinase Ia) is shown to be regulated through direct phosphorylation by CaM kinase I kinase (CaMKIK). In the present study, three distinct CaMKIK peaks were separated from Q-Sepharose colunm chromatography of pig brain homogenate using a Waters 650 Protein Purification System. The purified CaMKIK from the major peak potently and rapidly enhanced CaM kinase Ia activity, reaching a maximal stimulation within 2min at the concentrations of 12-15nM. The activated state of CaM kinase Ia is characterized by a markedly enhanced Vmax as well as significantly decreased Km and Ka values toward peptide substrate and CaM, respectively. These observations suggest the activation process of CaM kinase Ia. The phosphorylation of CaM kinase Ia by CaMKIK may induce its conformational change responsible for the alterations in the kinetic properties, which ultimately leads to the rapid enzyme activation.
조정숙(Jung Sook Cho),양재하(Chae Ha Yang),박창국(Chang Gook Park),이희순(Hee Soon Lee),김영호(Young Ho Kim) 대한약학회 2000 약학회지 Vol.44 No.1
The methanol extracts were prepared from 46 oriental medicines currently used for stroke treatment, and the effects were assessed on the excitotoxic neuronal cell death induced by L- glutamate(Glu) in primary cultured rat cortical neurons. The extracts from Angelicae gigantis Radix, Manitis Squama, Acori graminei Rhizoma, Uncariae RamWus et Uncus, Alpiniae Fructus, Paeoniae Radix, and Cnidii Rhizoma inhibited the Glu-induced neurotoxicity with the IC50 values of 95.2, 218.6, 263.3, 295.1, 297.9, 310.1, and 446.7mcg/ml, respectively. The extracts from Arisaematis Rhizoma, Loranthi Ramulus, Anemarrhenae Rhizoma, Carthami Flos, Clematidis Radix, Bambusae Concretio Silicea, and Angelicae koreanae Radix also exhibited significant inhibition of the toxicity. In contrast, the extracts from Aconiti Tuber, Araliae cordatae Radix, Curcumae Rhizoma, Leonuri Herba, Polygalae Radix, Salviae Radix, and Siegesbeckiae Herba increased the Glu-induced toxicity at the concentrations of 500 and 1000mcg/ml. Rest of the extracts evaluated in the present study showed minor or negligible inhibition. Taken together, the oriental medicines including Angeficae gigantis Radix, Manitis Squama, Acori graminei Rhizoma, Uncariae Rwnulus et Uncus, and Alpiniae Fructus appear to exert pharmacological effects through the inhibition of excitotoxic neuronal cell death. Further studies are in progress to characterize active principles in these extracts.
조정숙(Jung sook Cho) 대한약학회 2005 약학회지 Vol.49 No.1
Xuesaitong Ruanjiaonang (XR), a soft capsule containing Panax notoginseng saponins as main ingredients, is believed to remove extravasated blood and increase cerebral blood flow by improving blood circulation, and therefore, has been used in China to treat ischemic stroke or hemiplegia caused by cerebral thrombosis. To characterize pharmacological actions of XR, the present study evaluated its effects on neuronal cell damage induced by various oxidative insults or excitotoxic amino acids in primary cultured rat cortical cells. The neuronal cell viability was not affected by XR with the exposure for 2 h at the concentrations tested in this study (10~1000 ㎍/㎖). However, significant reduction of the cell viability was observed when the cultured cells were exposed to XR at 1000 ㎍/㎖ for 24 h. XR was found to concentration-dependently inhibit the oxidative neuronal damage induced by H2O2, xanthine/xanthine oxidase or Fe2+/ascorbic acid. In addition, it dramatically inhibited the excitotoxic damage induced by glutamate or N-methyl-D- aspartate (NMDA). We found that the NMDA-induced neurotoxicity was inhibited more effectively and potently than the glutamate-induced toxicity. Moreover, XR was found to exert mild inhibition of lipid peroxidation induced by Fe2+/ascorbic acid in rat brain homogenates and some 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate neuroprotective and antioxidant effects of XR, showing inhibition of oxidative and excitotoxic damage in the cultured cortical neurons, as well as inhibition of lipid peroxidation and its radical scavenging activity. Considering that excitotoxicity and oxidative stress play crucial roles in neuronal cell damage during ischemia and reperfusion, these results may provide pharmacological basis for its clinical usage to treat ischemic stroke.
조정숙 ( Jung Sook Cho ),박종숙 ( Jong Sook Park ),김희숙 ( Hy Sook Kim ) 대한임상검사과학회 2001 대한임상검사과학회지(KJCLS) Vol.33 No.2
Tumor diathesis is defmed as a host response to tissue destruction by infiltrative growth of cancer. It is observed in smears as eosinophilic or cyanophilic granular proteineous material, Cytoplasmic debris, hemosiderin, fi버11, nuclear fragments and cells with karyorrhexis. The purpose of this study was to determine the prevalence and cytologic features of tumor diathesis in cervicovaginal smears from patients with invasive squamous cell carcinoma. Cervicovaginal smears of 63 patients with squamous cell carcinoma histologically confmned were reviewed to evaluate the presence of macro/micro tumor diathesis(MaTD/MiTD). Original cytologic diagnoses were HSIL with carcinoma in situ in 21 cases(33.3%), microinvasive carcinoma in 13 cases(20.6%) and invasive carcinoma in 29 cases(46%). Tumor diathesis was posItive in 49 cases(77.8%), lltεgative in 10 cases(15.9%) of smears with invasive squamous cell carcinoma and 4 cases(6.3%) were undetermined. Both MaTD and MiTD were seen in 36 cases(73.5%), only MaTD was 9 cases(18.4%) and MiTD was 4 cases(8.2%). As increasing the invasion depth, prevalence of tumor diathesis was increased, but it was not statistically significant(p>O.OO5). Twelves of control group were diagnosed as invasive squamous cell carcinoma cytologically, but they were histologically confmned as carcinoma in situ. Tumor diathesis was positive in 9 cases(75%) of the 12 smears, it was supposed of intraglandular karyorrhetic necrotic material in the glandular involvement with carcinoma in situ. Although tumor diathesis is an important criterion of invasive carcinoma, the smear should be veη carefully searched the presence of invasive carcinoma cells.
흰쥐 미숙 대뇌피질 신경세포에서 quisqualate로 유발된 흥분성 세포독성에 대한 spermine의 영향
조정숙(Jung Sook Cho) 대한약학회 1999 약학회지 Vol.43 No.4
Glutamate (Glu) receptor-mediated excitotoxicity has been implicated in many acute and chronic types of neurological disorders. Exposure of mature rat cortical neurons (15~18 days in culture) to the various concentrations of Glu resulted in a marked neuronal death, whereas immature rat cortical neurons (4~5 days in culture) were resistant to the Glu-induced toxicity. Glu receptor subtype-specific agonists showed differential extent of toxicity in the immature neurons. The neurons treated with NMDA or kainate (KA) did not exhibit damage. However, quisqualate (QA) treatment induced a considerable cell death (36.1%) in immature neurons. The non-NMDA antagonist DNQX did not reduce this response. Interestingly, the QA-induced damage was not altered by the polyamine antagonist ifenprodil. Taken together, unlike NMDA or KA, QA can induce neurotoxicity in immature rat cortical neurons and the QA-induced toxicity was potentiated by spermine. The lack of antagonizing effects of DNQX and ifenprodil on QA-induced toxicity and the potentiated toxicity by spermine, respectively, implies that both QA receptor and the polyamine site of NMDA receptor may not mediate the neurotoxicity observed in this study, and that a distinct mechanism(s) may be involved in the excitotoxicity in immature neurons.