• Journal of Yeungnam Medical Science
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• 제41권2호
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• pp.61-73
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• 2024

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.69-79
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• 2002

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.617-628
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• 1998

In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.

• The Journal of Korean Physical Therapy
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• 제13권3호
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• pp.791-797
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• 2001

After brain injury, patients show a wide range in the degree of recovery. By a variety of mechanisms, the human brain is constantly undergoing plastic changes. Spontaneous recovery from brain injury in the chronic stage omes about because of plasticity. The brain regions are altered. resulting in functionally modified cortical network. This review cnsidered the neural plasticity from cellular and molecular mechanisms of synapse formation to behavioural recovery from brain injury in elderly humans. The stimuli required to elicit plasticity are thought to be activity-dependent elements. especially exercise and learning. Knowledge about the physiology of brain plasticity has led to the development of methods for rehabilitation.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.245-251
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• 2008

Single-channel recordings of TASK-1 and TASK-3, members of two-pore domain $K^+$ channel family, have not yet been reported in dorsal root ganglion (DRG) neurons, even though their mRNA and activity in whole-cell currents have been detected in these neurons. Here, we report single-channel kinetics of the TASK-3-like $K^+$ channel in DRG neurons and up-regulation of TASK-3 mRNA expression in tissues isolated from animals with spinal cord injury (SCI). In DRG neurons, the single-channel conductance of TASK-3-like $K^+$ channel was $33.0{\pm}0.1$ pS at - 60 mV, and TASK-3 activity fell by $65{\pm}5%$ when the extracellular pH was changed from 7.3 to 6.3, indicating that the DRG $K^+$ channel is similar to cloned TASK-3 channel. TASK-3 mRNA and protein levels in brain, spinal cord, and DRG were significantly higher in injured animals than in sham-operated ones. These results indicate that TASK-3 channels are expressed and functional in DRG neurons and the expression level is up-regulated following SCI, and suggest that TASK-3 channel could act as a potential background $K^+$ channel under SCI-induced acidic condition.

• Tuberculosis and Respiratory Diseases
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• 제54권5호
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• pp.522-531
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• 2003

연구배경 : 급성 폐손상을 일으키는 요인중의 하나인 출혈성쇼크시 나타나는 급성 폐손상의 양상과 아스피린이 이에 미치는 효과를 알아보고자 본 연구를 시행하였다. 방법 : 실험동물은 체중 350g 내외의 Sprague-Dawley 종흰쥐를 사용하였고, 혈압측정 및 출혈을 시키기 위하여 catheter를 양쪽 대퇴동맥에 삽입하였다. 수술 후 polygraph를 이용하여 평균동맥압을 기록하였으며, 출혈은 withdrawal pump를 이용하여 5분간 체중 kg 당 20 ml의 혈액을 출혈시켰다. 실험군은 대조군, 출혈군과 아스피린 처치군으로 분류하였다. 대조군은 출혈군과 동일하게 수술하고 출혈은 시키지 않았으며 나머지 과정은 출혈군과 동일하게 처리하였다. 아스피린 처치군은 출혈 30분전 대퇴정맥으로 아스피린 (10mg/kg)을 주입하였고, 출혈군은 체중 당 동일한 양의 생리식염수를 주입하였다. 이상의 처치 후 2시간 또는 24시간 동안 cage에서 자유롭게 활동하도록 하였으며, 출혈후의 폐손상 정도와 아스피린이 이에 미치는 효과를 알아보기 위하여 폐장내 myeloperoxidase 활성도와 폐세척액 내의 단백함량과 백혈구 수를 측정하였다. 결과 : 폐장내 myeloperoxidase 활성도와 폐세척액 내의 단백함량과 백혈구수는 출혈 2시간 및 24시간 후 대조군에 비해 유의하게 증가하였다. 이러한 반응은 아스피린 전처치에 의하여 효과적으로 차단되었다. 결론 : 이상의 결과로 심한 출혈 후에 급성 폐손상이 생길 수 있으며 이는 아스피린 전처치로 효과적으로 예방될 수 있다고 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.329-334
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• 2019

Diabetes is associated with an increased risk of cardiovascular complications. Dipeptidyl peptidase-4 (DPP-IV) inhibitors are used clinically to reduce high blood glucose levels as an antidiabetic agent. However, the effect of the DPP-IV inhibitor gemigliptin on ischemia/reperfusion (I/R)-induced myocardial injury and hypertension is unknown. In this study, we assessed the effects and mechanisms of gemigliptin in rat models of myocardial I/R injury and spontaneous hypertension. Gemigliptin (20 and 100 mg/kg/d) or vehicle was administered intragastrically to Sprague-Dawley rats for 4 weeks before induction of I/R injury. Gemigliptin exerted a preventive effect on I/R injury by improving hemodynamic function and reducing infarct size compared to the vehicle control group. Moreover, administration of gemigliptin (0.03% and 0.15%) powder in food for 4 weeks reversed hypertrophy and improved diastolic function in spontaneously hypertensive rats. We report here a novel effect of the gemigliptin on I/R injury and hypertension.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.405-414
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• 1999

The role of platelet-activating factor (PAF) was investigated in intestinal ischemia/reperfusion (I/R) induced acute lung injury associated with oxidative stress. To induce acute lung injury following intestinal I/R, superior mesenteric arteries were clamped with bulldog clamp for 60 min prior to the 120 min reperfusion in Sprague-Dawley rats. Acute lung injury by intestinal I/R was confirmed by the measurement of lung leak index and protein content in bronchoalveolar lavage (BAL) fluid. Lung leak and protein content in BAL fluid were increased after intestinal I/R, but decreased by WEB 2086, the PAF receptor antagonist. Furthermore, the pulmonary accumulation of neutrophils was evaluated by the measurement of lung myeloperoxidase (MPO) activity and the number of neutrophils in the BAL fluid. Lung MPO activity and the number of neutrophils were increased (p＜0.001) by intestinal I/R and decreased by WEB 2086 significantly. To confirm the oxidative stress induced by neutrophilic respiratory burst, gamma glutamyl transferase (GGT) activity was measured. Lung GGT activity was significantly elevated after intestinal I/R (p<0.001) but decreased to the control level by WEB 2086. On the basis of these experimental results, phospholipase $A_2\;(PLA_2),$ lysoPAF acetyltransferase activity and PAF contents were measured to verify whether PAF is the causative humoral factor to cause neutrophilic chemotaxis and oxidative stress in the lung following intestinal I/R. Intestinal I/R greatly elevated $PLA_2$ activity in the lung as well as intestine (p<0.001), whereas WEB 2086 decreased $PLA_2$ activity significantly (p<0.001) in both organs. LysoPAF acetyltransferase activity, the PAF remodelling enzyme, in the lung and intestine was increased significantly (p<0.05) also by intestinal I/R. Accordingly, the productions of PAF in the lung and intestine were increased (p<0.001) after intestinal I/R compared with sham rats. The level of PAF in plasma was also increased (p<0.05) following intestinal I/R. In cytochemical electron microscopy, the generation of hydrogen peroxide was increased after intestinal I/R in the lung and intestine, but decreased by treatment of WEB 2086 in the lung as well as intestine. Collectively, these experimental results indicate that PAF is the humoral mediator to cause acute inflammatory lung injury induced by intestinal I/R.

• Tuberculosis and Respiratory Diseases
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• 제51권6호
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• pp.503-516
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• 2001

연구배경 : 급성 출혈성 쇼크에서 발생하는 급성폐손상의 병인론을 호중구의 산소기 생성과 연관하여 규명하고자 본 연구를 시행하였다. 급성출혈성쇼크에서 폐장내 산소기 생성의 주된 원인이 호중구의 침윤에 의한 것이며 이 때 PLA2의 활성화가호중구의 respiratory burst의 직접적인 원인임올 밝히고지 하였다. 방 법 : 체중 300-350 g 정도의 흰쥐에서 체중/kg 당 20ml정도의 혈액을 5분 동안 뽑아내어 급성 출혈성 쇼크를 유발하고 이 출혈성 쇼크 상태를 1시간 동안 유지하였다. 그 후 급성 폐손상의 지표들을 측정하였다. 동시에 폐장의 미세구조의 변화 및 세포화학적인 검사를 통하여 폐장조직내의 산소기의 형성을 확인하였다. 또한 PLA2 억제제인 mepacrine을 출혈직전에 투여하여 PLA2의 억제에 따른 변화도 검사, 비교하였다. 결 과 : 급성 출혈성 쇼크에 의해 유도된 급성 폐손상에서 호중구의 폐장내 침윤이 확인되었고 이 때 폐부종 및 조직내 산소기 형성의 증가가 관찰되었으며, 폐장내 PLA2의 활성도도 증가하였다. 그러나 mepacrine을 이용하여 PLA2를 억제한 결과, 폐부종의 감소, 산소기 형성의 감소가 확인되었다. 결 론 : 급성 출혈성 쇼크에 의한 급성폐손상은 호중구에 의한 산화성스트레스가 그 원인으로 생각되고 이 때 호중구에 의한 산화성스트레스의 발생에는 PLA2가 주된 역할을 한다고 사료된다.

• International Journal of Oral Biology
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• 제37권3호
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• pp.121-129
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• 2012

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the antiallodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 ${\mu}g$ of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 ${\mu}g$) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant antinociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.