• Proceedings of the PSK Conference
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• 2002.10a
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• pp.297.3-298
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• 2002

A benzopyranyl derivative. KR32000. synthesized as a plausible KATP opener. has been shown to exert cardioprotective effect in vivo myocardial infarct model. In this study. we investigated whether KR32000 can produce cardioprotective effect against hypoxia- and reactive oxygen species(ROS)-induced injury in heart-derived H9c2 cells. Hypoxic injury was induced by incubating cells in anaerobic chamber (glucose-free. serum-free DMEM. 85% N2. 5% CO2. 10% H2) and oxidative stress was induced by buthionine sulfoximine(BSO). (omitted)

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.37-41
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• 2018

Mitochondrial injury in renal tubule has been recognized as a major contributor in acute kidney injury (AKI) pathogenesis. Ischemic insult, nephrotoxin, endotoxin and contrast medium destroy mitochondrial structure and function as well as their biogenesis and dynamics, especially in renal proximal tubule, to elicit ATP depletion. Mitochondrial fatty acid ${\beta}$-oxidation (FAO) is the preferred source of ATP in the kidney, and its impairment is a critical factor in AKI pathogenesis. This review explores current knowledge of mitochondrial dysfunction and energy depletion in AKI and prospective views on developing therapeutic strategies targeting mitochondrial dysfunction in AKI.

• Tuberculosis and Respiratory Diseases
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• v.68 no.2
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• pp.55-61
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• 2010

Background: The underlying pathogenesis of fat embolism-induced acute lung injury (ALI) has not been elucidated. In the present study, the pathogenesis of fat embolism-induced ALI was probed in association with neutrophilic oxidative stress in oleic acid (OA)-induced ALI of S-D rats. Methods: OA was injected intravenously to provoke ALI in experimental rats. Five hours later, indices of ALI were measured to confirm the role of the neutrophilic respiratory burst. The effect of an inhibition of phospholipase A2 (PLA2) was also evaluated. Results: The accumulation of neutrophils in the lung due to OA caused increased neutrophilic oxidative stress in lung, which was ameliorated by mepacrine. What were the results from inhibition of PLA2. Conclusion: Excess neutrophilic oxidative stress contributes to OA-induced ALI, which is lessened by the inhibition of PLA2.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.5
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• pp.253-257
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• 2004

Schwann cells play an important role in peripheral nerve regeneration. Upon neuronal injury, activated Schwann cells clean up the myelin debris by phagocytosis, and promote neuronal survival and axon outgrowth by secreting various neurotrophic factors. However, it is unclear how the nerve injury induces Schwann cell activation. Recently, it was reported that certain cytoplasmic molecules, which are secreted by cells undergoing necrotic cell death, induce immune cell activation via the toll-like receptors (TLRs). This suggests that the TLRs expressed on Schwann cells may recognize nerve damage by binding to the endogenous ligands secreted by the damaged nerve, thereby inducing Schwann cell activation. Accordingly, this study was undertaken to examine the expression and the function of the TLRs on primary Schwann cells and iSC, a rat Schwann cell line. The transcripts of TLR2, 3, 4, and 9 were detected on the primary Schwann cells as well as on iSC. The stimulation of iSC with poly (I : C), a synthetic ligand for the TLR3, induced the expression of $TNF-{\alpha}$ and RANTES. In addition, poly (I : C) stimulation induced the iNOS expression and nitric oxide secretion in iSC. These results suggest that the TLRs may be involved in the inflammatory activation of Schwann cells, which is observed during Wallerian degeneration after a peripheral nerve injury.

• The Korean Journal of Physiology
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• v.28 no.1
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• pp.71-77
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• 1994

In the animal model of acute respiratory distress syndrome (ARDS) induced by N-nitroso-N-methylurethane (NNNMU) the secretory activity of alveolar type H cells during acute alveolar injury was investigated by determining phospholipid and pulmonary surfactant associated proteins in crude surfactant. The mechanism of the secretory change was studied by determination of DNA and RNA levels in the lung tissue. After induction of acute alveolar injury with NNNMU, pulmonary hemorrhage, atelectasis and gross hypertrophy were observed. Seven days after NNNMU treatment the level of total DNA in lung homogenate was increased markedly indicating that a hypertrophy was induced by cellular proliferation. Although the total DNA level increased, the RNA/DNA ratio was gradually decreased after NNNMU treatment. Seven days after NNNMU treatment the RNA/DNA ratio returned to the normal control level. During the acute alveolar injury, phospholipid and surfactant associated proteins were reduced significantly as compared with the control, implying that the secretory activity of alveolar type II cells was altered during acute alveolar injury induced by NNNMU. The protein content in crude surfactant during peak injury(7 days after NNNMU) was decreased significantly but phospholipid/protein ratios were identical in both control and NNNMU treatment groups. SDS-PAGE of proteins in crude pulmonary surfactant showed a decrease in major surfactant associated protein(M.W. 38,000) during acute alveolar injury. The present study may suggest that while alveolar type H cells proliferate markedly, transcription of alveolar type ll cell gene was inhibited by an unknown mechanism such as DNA methylation induced by NNNMU. Such an inhibition of transcriptional activity is thought to be associated with the decreased secretory activity of alveolar type ll cells, which may lead to pulmonary atelectasis and edema during the acute alveolar injury.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.59-69
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• 2010

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists ($1{\mu}g$ bicuculline/rat and $5{\mu}g$ phaclofen/rat), agonists ($1{\mu}g$ muscimol/rat and $0.5{\mu}g$ baclofen/rat) or GABA transporter (GAT) inhibitors ($20{\mu}g$ NNC-711/rat and $1{\mu}g$ SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.156-163
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• 2000

Background: Peripheral nerve injury sometimes leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia have a sympathetically maintained pain which is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for cold-evoked pain that is sympathetically dependent is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating cold-evoked pain that developed following peripheral nerve injury. Methods: Neuropathic surgery was performed by a unilateral ligation of L5 and L6 spinal nerves of rats. Behavioral sign of cold-evoked pain was examined for 5 min by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold temperature ($5^{\circ}C$). Whether cold-evoked pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated. Results: After ligation, duration of foot lifting on the ligated side at cold temperature increased as compared to the pre-operative period. This increase maintained for the entire 40-day test period. Pretreatment with alpha-antagonist phentolamine produced a suppression of cold-evoked pain behavior that was not affected by beta-antagonist propranolol pretreatment. Prazosin, alpha-1 antagonist, suppressed cold- evoked pain behavior when treated either before or after nerve ligation. On the other hand, alpha-2 antagonist yohimbine was without effect on cold-evoked pain behavior whether it was treated before or after the ligation. Conclusions: The results suggest that peripheral nerve injury develops cold-evoked pain that is sympathetically dependent, and that alpha-1 adrenoreceptor plays a critical role for the generation of this type of pain in its initiation as well as maintenance.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.331-343
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• 1998

Sublethal dose of bacterial lipopolysaccharide (LPS) would induce protection against cardiac ischemic/reperfusion (I/R) injury. This study examines the following areas: 1) the temporal induction of the cardio-protection produced by LPS; and 2) the relations between a degree of protection and the myocardial prostacyclin ($PGI_2$) production. Rats were administered LPS (2 mg/kg, i.v.), and hearts were removed 1, 4, 8, 14, 24, 48, 72,and 96 h later. Using Langendorff apparatus, haemodynamic differences during 25 min of global ischemia/30 min reperfusion were investigated. The concentration of $PGI_2$ in aliquots of the coronary effluent was determined by radioimmunoassay as its stable hydrolysis product $6-keto-PGF1_{\alpha}$ and lactate dehydrogenase release were measured as an indicative of cellular injury. LPS-induced cardiac protection against I/R injury appeared 4 h after LPS treatment and remained until 96 h after treatment. $PGI_2$ release increased 2-3 fold at the beginning of reperfusion compared to basal level except in hearts treated with LPS for 48 and 72 h. In hearts removed 48 and 72 h after LPS treatment, basal $PGI_2$ was increased. To determine the enzymatic step in relation to LPS-induced basal $PGI_2$ production, we examined prostaglandin H synthase (PGHS) protein expression, a rate limiting enzyme of prostaglandin production, by using Western blot analysis. LPS increased PGHS protein expression in hearts at 24, 48, 72, 96 h after LPS treatment. Induction of PGHS expression appeared in both isotypes of PGHS, a constitutive PGHS-1 and an inducible PGHS-2. To identify the correlationship between $PGI_2$ production and the cardioprotective effect against I/R injury, indomethacin was administered in vivo or in vitro. Indomethacin did not inhibit LPS-induced cardioprotection, which was not affected by the duration of LPS treatment. Taken together, our results suggest that $PGI_2$ might not be the major endogenous mediator of LPS-induced cardioprotection.

• BMB Reports
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• v.48 no.3
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• pp.184-189
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• 2015

Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) is known to protect neurons from neurodegeneration during ischemia/reperfusion injury. We recently reported that ROS-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 in astrocytes and complex formation between caveolin-1 and SHP-2 in response to oxidative stress. To examine the region of SHP-2 participating in complex formation with caveolin-1, we generated three deletion mutant constructs and six point mutation constructs of SHP-2. Compared with wild-type SHP-2, binding of the N-SH2 domain deletion mutant of SHP-2 to p-caveolin-1 was reduced greatly, using flow cytometric competitive binding assays and surface plasmon resonance (SPR). Moreover, deletion of the N-SH2 domain of SHP-2 affected $H_2O_2$-mediated ERK phosphorylation and Src phosphorylation at Tyr 419 in primary astrocytes, suggesting that N-SH2 domain of SHP-2 is responsible for the binding of caveolin-1 and contributes to the regulation of Src phosphorylation and activation following ROS-induced oxidative stress in brain astrocytes.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.289-297
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• 1996

Excitatory amino acids (EAA) are thought to play an important role in producing cell death associated with ischemic and traumatic spinal cord injury. The present study was carried out to determine if the response characteristics of spinal sensory neurons in segments adjacent to degeneration sites induced by EAA are altered following these morphological changes. Intraspinal injections of quisqualic acid (QA) produced neuronal degeneration and spinal cavitation of gray matter. The severity of lesions was significantly attenuated by pretreatment with a non-NMDA antagonist NBQX. In extracellular single unit recordings, dorsal horn neurons in QA injected animal showed the increased mechanosensitivity, which included a shift to the left in the stimulus-response relationship, an increased background activity and an increase in the duration of after-discharge responses. Neuronal responses, especially the C-fiber response, to suprathreshold electrical stimulation of sciatic nerve also increased in most cases. These results suggest that altered functional states of neurons may be responsible for sensory abnormalities, e.g. allodynia and hyperalgesia, associated with syringomyolia and spinal cord injury.