Generation of Superoxide Radical from Rat Brain Mitochondria and Mechanism of Its Toxic Action to Mitochondrial and Extra-mitochondrial Components

노재규,표장근,정명희,임정규,명호진,Roh, Jae-Kyu,Pyo, Jang-Geun,Chung, Myung-Hee,Lim, Jung-Kyoo,Myung, Ho-Jin The Korean Society of Pharmacology 1985 대한약리학잡지 Vol.21 No.1

흰쥐 뇌 미토콘드리아에 의한 $O^{-}_{2}{\cdot}$ 의 생성과 이 radical의 유해작용 및 그 작용기전을 알아보기 위하여 본실험을 수행하였다. Succinate와 antimycin존재하에서 미토콘드리아는 $O^{-}_{2}{\cdot}$을 생성하였으며 이는 SOD-inhibitable NBT환원으로 확인되었다. 동일 조건에서 $H_2O_2$는 일차생성물인 $O^{-}_{2}{\cdot}$의 dismutation으로 생성됨을 알수 있었다. 상기조건에서 미토콘드리아의 막지질이 파괴되었고 반응액에 첨가된 isocitrate dehydrogenase와 적혈구에 각각 불활성화와 용혈이 초래되었다. 이같은 작용은 $Fe^{++}$이 있을때만 관찰 되었다. 그리고 독작용은 superoxide dismutase 혹은 castalase에 의해서 억제되었다. 또한 methional을 첨가하였을 때 ethylene이 생성되었으며 그 생성은 $Fe^{++}$에 의하여 현저히 증가하였다. Ethylene 생성 역시 상기 효소에 의하여 억제되었다. 따라서 미토콘드리아에서 발생된 $O^{-}_{2}{\cdot}$은 거대분자 및 세포에 독성을 나타낼수 있으며 이같은 작용은 $Fe^{++}$의 촉매작용에 의한 $O^{-}_{2}{\cdot}$와 $H_2O_2$의 상호작용으로 발생되는 $OH{\cdot}$ 에 의한것으로 추측되었다. 이상의 결과는 미토콘드리아가 유독성 산소 radical을 발생하므로 조직손상을 시킬 수 있다는 가능성을 시사하는 증거라고 생각되었다. The generation of $O^{-}_{2}{\cdot}$ and its toxic effects were studied with rat brain mitochondria. The production of $O^{-}_{2}{\cdot}$ from mitochondria in the presence of succinate and antimycin was demonstrated by SOD-inhibitable reduction of NBT. Although succinate can support the $O^{-}_{2}{\cdot}$ formation, the highest rate needs antimycin indicating that blockade of electron flow in the respiratory chain augments the univalent reduction of molecular oxygen. Under this condition, $H_2O_2$ was also observed to be produced. But its formation appears to be derived from the dismutation of the primary product, $O^{-}_{2}{\cdot}$ since the rate of $H_2O_2$ production was markedly decreased by NBT and ferricytochrome c. The $O^{-}_{2}{\cdot}$ and $H_2O_2$ produced were able to cause toxic actions to mitochondrial and extra-mitochondrial components as shown by lipid peroxidation of mitochondrial membrane, and inactivation and lysis of isocitrate dehydrogenase and erythrocytes added to the medium, respectively. In all the toxic actions observed, $Fe^{++}$ was required. It appears that in the toxic actions $OH{\cdot}$ generated from the iron-catalyzed Haber-Weiss reaction acts as a mediator. This was supported by the finding that mitochondria in the presence of succinate and antimycin produced ethylene from methional, and $Fe^{++}$ added increased the ethylene production. The observed toxic actions of mitochondrial $O^{-}_{2}{\cdot}$ may provide evidence supporting a potential role of mitochondria as a source of oxygen radicals to cause tissue damage.

흰쥐 뇌 미토콘드리아에 의한 superoxide radical의 생성과 이 radical이 미토콘드리아 및 미토콘드리아 외 물질에 대한 독작용과 그 기전에 관한 연구

노재규(Jae-Kyu Roh),표장근(Jang-Geun Pyo),정명희(Myung-Hee Chung),임정규(Jung-Kyoo Lim),명호진(Ho-Jin Myung) 대한약리학회 1985 대한약리학잡지 Vol.21 No.1

흰쥐 뇌 미토콘드리아에 의한 O₂^-⋅ 의 생성과 이 radical의 유해작용 및 그 작용기전을 알아보기 위하여 본실험을 수행하였다. Succinate와 antimycin존재하에서 미토콘드리아는 O₂^-⋅을 생성하였으며 이는 SOD-inhibitable NBT환원으로 확인되었다. 동일 조건에서 H₂O₂는 일차생성물인 O₂^-⋅의 dismutation으로 생성됨을 알수 있었다. 상기조건에서 미토콘드리아의 막지질이 파괴되었고 반응액에 첨가된 isocitrate dehydrogenase와 적혈구에 각각 불활성화와 용혈이 초래되었다. 이같은 작용은 Fe⁺⁺이 있을때만 관찰 되었다. 그리고 독작용은 superoxide dismutase 혹은 castalase에 의해서 억제되었다. 또한 methional을 첨가하였을 때 ethylene이 생성되었으며 그 생성은 Fe⁺⁺에 의하여 현저히 증가하였다. Ethylene 생성 역시 상기 효소에 의하여 억제되었다. 따라서 미토콘드리아에서 발생된 O₂^-⋅은 거대분자 및 세포에 독성을 나타낼수 있으며 이같은 작용은 Fe⁺⁺의 촉매작용에 의한 O₂^-⋅와 H₂O₂의 상호작용으로 발생되는 OH⋅ 에 의한것으로 추측되었다. 이상의 결과는 미토콘드리아가 유독성 산소 radical을 발생하므로 조직손상을 시킬 수 있다는 가능성을 시사하는 증거라고 생각되었다. The generation of O₂^-⋅ and its toxic effects were studied with rat brain mitochondria. The production of O₂^-⋅ from mitochondria in the presence of succinate and antimycin was demonstrated by SOD-inhibitable reduction of NBT. Although succinate can support the O₂^-⋅ formation, the highest rate needs antimycin indicating that blockade of electron flow in the respiratory chain augments the univalent reduction of molecular oxygen. Under this condition, H₂O₂ was also observed to be produced. But its formation appears to be derived from the dismutation of the primary product, O₂^-⋅ since the rate of H₂O₂ production was markedly decreased by NBT and ferricytochrome c. The O₂^-⋅ and H₂O₂ produced were able to cause toxic actions to mitochondrial and extra-mitochondrial components as shown by lipid peroxidation of mitochondrial membrane, and inactivation and lysis of isocitrate dehydrogenase and erythrocytes added to the medium, respectively. In all the toxic actions observed, Fe⁺⁺ was required. It appears that in the toxic actions OH⋅ generated from the iron-catalyzed Haber-Weiss reaction acts as a mediator. This was supported by the finding that mitochondria in the presence of succinate and antimycin produced ethylene from methional, and Fe⁺⁺ added increased the ethylene production. The observed toxic actions of mitochondrial O₂^-⋅ may provide evidence supporting a potential role of mitochondria as a source of oxygen radicals to cause tissue damage.

신경줄기세포의 혈관내 이식법

주건 ( Kon Chu ),신동인 ( Dong In Sin ),노재규 ( Jae Kyu Roh ) 한국조직공학과 재생의학회 2005 조직공학과 재생의학 Vol.2 No.4

Neural stem cells (NSCs) are the most primordial and least committed cells of the nervous system, the cells that exist before regional/functional specification develops. NSCs have the following functional properties: (1) multipotency, (2) the ability to populate a developing region and/or repopulate an ablated or degenerated region of the nervous system with appropriate cell types, (3) the ability to be serially transplanted, and (4) Self-renewal. Recent experiments have shown that NSCs can be transplanted in many neurological disorder models (ischemia, hemorrhage, epilepsy, Parkinsonism, brain tumor, Huntington`s disease, multiple sclerosis, peripheral neuropathy, spinal cord injury, and motor neuron diseases) and can ameliorate the pathogenic insult. This review focuses on the transplantation efficacy in stroke, and optimization strategy for achieving better outcome, considering the pathogenesis of specific diseases.

파킨슨병에서 99mTc - HMPAO SPECT를 이용한 국소뇌혈류의 정량적 분석

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이명혜(Myung Hae Lee),노재규(Jae Kyu Roh),명호진(Ho Jin Myung),배상균(Sang Kyun Bae) 대한핵의학회 1992 핵의학 분자영상 Vol.26 No.2

N/A Regional cerebral blood flow were measured in 10 patients with Parkinson's disease and 12 normal persons using Tc-99m-HMPAO SPECT. Reconstructed images were interpreted qualitatively and were compared with those findings of CT. For the quantitative analysis, six pairs of region of interest matched with the perfusion territories of large cerebral arteries and cerebellar hemisphere were determined. From the count values, indices showing the degree of asymmetry between right and left cerebral or cerebellar hemisphere, cerebral asymmetry index (ASI) and percent index of cerebellar asymmetry (PIA), and an index showing change of each region, region to cerebellum ratio (RCR) were obtained. ASI of normal persons and patients were 0.082±0.033 and 0.108±0.062, respectively and PIA were -0.4±0.7% and -0.7±1.0%, respectively, which showed no statistically significant difference between normal persons and patients. Among 10 RCR's, those of both regions of basal ganglia and both regions of anterior cerebral artery were significantly reduced. We concluded that the most significant reduction of regional cerebral blood flow in patients with Parkinson's disease was observed in the regions of basal ganglia and in the regions of anterior cerebral artery, and the degree of change in hemispheric blood flow was similar in both hemisphere.

Thallium - 201 SPECT 뇌종양 영상

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),김상은(Sang Eun Kim),최창운(Chang Woon Choi),노재규(Jae Kyu Roh),정희원(Hee Won Jung),윤병우(Byung Woo Yoon) 대한핵의학회 1992 핵의학 분자영상 Vol.26 No.1

N/A Thal1ium-201 (201TI) SPECT Studies were performed on a normal volunteer and 12 patients with intracerebral lesions: 3 patients with gliomas, 3 patients with meningiomas, 1 patient each with metastatic tumor, brain abscess, and cerebral infarction, and 3 postirradiation patients. (2 with metastatic tumors, I with lymphoma). A 201T1 index, based on the ratio of 201T1 uptake in the brain lesion Versus the homologous contralateral brain, was calculated and compared with tumor histology and CT/MRI findings. The SPECT 201T1 Scan showed minimal uptake of tracer in a normal brain. There was substantial uptake of 201T1 in high-grade gliomas (index〉l.5) with little uptake in low-grade lesions. A previously irradiated patient with recurrent astrocytoma, in whom MRI study was unable to distinguish tumor recurrence from necrosis, showed the lesions with high 201T1 indices in both hemispheric regions (2.50/1.93), suggesting tumor recurrence. Two meningiomas and a metastatic tumor showed varying degrees of 201T1 uptake (index 1.71-8.15), revealing that 201Tl uptake is not exclusive to high-grade gliomas. In 2 postirradiation patients with metastatic tumors, no abnormal 201T1 uptake was found in the cerebral lesions, shortly after the initiation of radiation therapy or despite the persistence of enhancing lesions-though improved-on MR images, suggesting that 201T1 uptake may reflect the metabolic and possibly clonogenic activities of tumors and the brain 201T1 SPECT imaging might be valuable for the evaluation of tumor responsiveness to the therapy and for early detection of tumor recurrence. A patient with brain abscess on antibiotic treatment, showing increased uptake of 201T1 in the resolving lesions(index 2.87/1.52) is discussed. In a patient with cerebral infaraction, there was no abnormal uptake of 201T1 in infarcted tissue. When using a threshold index of 1.5, correlation rate between 201T1 uptake and contrast enhancement of the cerebral lesions on CT/MRI was 73%(8/11). In conclusions, the brain 201T1 SPECT imaging may be useful for assessment of tumor response to the therapy and to predict low or high-grade lesions.

99mTc - HMPAO SPECT를 이용한 정상인 국소뇌혈류의 정량적 분석

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),문대혁(Dae Hyuk Moon),궁성수(Sung Soo Koong),노재규(Jae Kyu Roh),명호진(Ho Jin Myung),이범우(Bum Woo Lee),이경한(Kyung Han Lee),최윤호(Yoon Ho Choi),윤병우(Byung Wo 대한핵의학회 1989 핵의학 분자영상 Vol.23 No.2

N/A Regional cerebral perfusion was evaluated in 15 normal controls by single photon emission comput- ed tomography using Tc HM-PAO. For quantitative analysis, 13 pairs of hornologous region of interest (ROI) were drawn on three transverse slices matching the vascular territories and cerebral cortices, and normal values of '3 semiqunatitative indices including Right to left ratio (R/L ratio), 'Regional index' (RI), and 'Region to cerebellum ratio (R/cbll ratio) were calculated. Mean values of R/L ratios of homologous regions were ranged frorn 0.985 to 1.023, and mean +- 2 s.d. of ali regions did not exceed 11% of mean. Significant difference of Rls (mean count per voxel of a ROJ/mean count per voxel of total ROls) between regions were found (p<0.001) with highest values in occipital cortex and cerebellum. After attenuation correction, Rls in deep gray, cranial portion of anterior cerebral artery and vascular territories in the 2nd siice increased significantly (p< 0.05 0.001). hut vise versa in other ROIs. Reginn to cerebellum ratios also showed regional difference siinifar to Rls.

국소뇌허혈에서 NMDA 수용체 길항제가 국소 뇌포도당 대사율에 미치는 영향

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),김상은(Sang Eun Kim),최창운(Chang Woon Choi),노재규(Jae Kyu Roh),윤병우(Byung Woo Yoon),홍승봉(Seung Bong Hong),배상균(Sang Kyun Bae) 대한핵의학회 1995 핵의학 분자영상 Vol.29 No.3

N/A There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuropro- tective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (1CGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[14C]glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded 1CGU ratio in 7 and 5 of the 15 regions measured, respectively(most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in 1CCPU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 postreatment did not significantly increase 1CGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

99mTc - HMPAO SPECT를 이용한 어린이 국소뇌혈류의 정량적 분석 : 정량적 지표들의 참고값 및 연령에 따른 변화

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),김상은(Sang Eun Kim),노재규(Jae Kyu Roh),명호진(Ho Jin Myung),윤병우(Byung Woo Yoon),조수철(Soo Churl Cho),홍승봉(Seung Bong Hong) 대한핵의학회 1991 핵의학 분자영상 Vol.25 No.1

N/A Regional cerebral blood flow (rCBF) was evaluated in 12 children ranging in age from 2.7 to 10.0 yr using 99mTc-HMPAO SPECT. For quantitative analysis, 13 pairs of homologous regions of interest (ROIs) were created on three attenuation-corrected 18,8 mm thick transverse slices matching the cerebral cortical regions, deep gray matter, cerebellar hemisphere, and vascular territories, and the semiquantitative indices including right to left ratio [(mean countjvoxel of homologous right ROI) /(mean count/voxel of homologous left ROI) ] and regional index (RI) [ (mean count/voxel of a ROI) /(rnean count/voxel of all ROIs of each hemisphere)] were calculated. Mean values of right to left ratios of homologous tegions ranged frorn 0.984 to 1.028 in children under 5 yr (group 1) and from 0.982 to 1.012 in children between 5 and 10 yr (group 2), and the mean value +-2 S.D. for each region did not exceed 11%. and 12% in group 1 and group 2, respective]y. There were no statis- tically significant differences between the RIs of the homologous right and left regions. Significant differences of RIs were found both between vascular regions (p<0,0005 for goup 1, and p=0,0001 for goup 2) and between regions of cerebral cortices (p<0,0005 for group 1, and p<0,005 for group 2) with a relatively high value in the occipital cortex and the Iower values in the r.erebellum and deep gray matter among the regions of cerebral cortices in both groups. There were no significant differences between the Rls of corresponding regions of group 1 and group 2, except a significantly higher value of right deep gray matter in group 2 than in group 1(p=0.0301). The RIs of the superior frontal cortex and deep gray matter showed to be positively correlated with age (superior frontal cortex; right: rs=0.5254, p =0.0814, left: rs=0.5919, p=0.0496/deep gray matter; right: rs=0.8246, p=0.0062, left: rs=0.6266, p=0,0377). The results suggest that the rCBF pattern of children approaches that of adults in an occipito-rostraJ direction. This time course of rCBF changes is in agreement with behavioral, neurophysiological, and anatomical alterations known to occur in the developing brain.

기저핵출혈의 동측에 발생한 편측 무도병 1예

오종배,김한준,전범석,노재규,노재규 대한신경과학회 1999 대한신경과학회지 Vol.17 No.5

양성 및 비양성 뇌교출혈의 임상방사선학적 연구

김병곤,이한보,박성호,노재규,노재규 대한신경과학회 1999 대한신경과학회지 Vol.17 No.1