Seong-Keun Moon

Activation of caspase cascades in Korean mistletoe (Viscum album var. coloratum) lectin-II-induced apoptosis of human myeloleukemic U937 cells.

Mistletoe lectins are of high biological activity and exert cytotoxic effects. We have previously shown that Korean mistletoe, Viscum album var. coloratum, lectin-II specifically induces apoptotic cell death in cancer cells, not normal lymphocytes. The destructive mechanism by mistletoe lectins on tumor cells was mediated by activation of c-JUN N-terminal kinase (JNK)/stress-activated protein kinase. Herein, we investigated the involvement of caspase cascade and its proteolytic cleavage effects on biosubstrates of human myeloleukemic U937 cells by D-galactoside and N-acetyl-galactosamine-specific Korean mistletoe lectin-II. Mistletoe lectin-II induced ladder pattern DNA fragmentation and activation of caspase-3, -8, and -9 of U937 cells, but not caspase-1 protease, in a time- and dose-dependent manner. Consistent with catalytic activation of protease, both poly(ADP-ribose) polymerase (PARP) and protein kinase C-delta (PKC-delta) are also cleaved in mistletoe lectin-II-treated U937 cells. An inhibitor of caspase-3-like protease, DEVD-CHO peptide, significantly inhibited mistletoe lectin-II-induced apoptosis, PARP cleavage, and fragmentation of DNA. These results provide the evidence that Korean mistletoe lectin-II induces apoptotic death of U937 cells via activation of caspase cascades.

Effect of prolonged cortical stimulation differs with size of infarct after sensorimotor cortical lesions in rats.

Motor deficit improvement is limited in rats with a large sensorimotor cortex infarct, even with cortical stimulation during rehabilitation. However, we find prolonged stimulation that differs with the size of cortical lesion to be effective. Two weeks of prolonged epidural electrical stimulation and rehabilitative training were delivered to rats whose cortex had been subjected to photothrombotic infarct after training in a single-pellet reaching task. Continuous stimulation greatly improved recovery in animals with large infarcts (6 mm diameter), while intermittent stimulation was more effective in animals with small (4 mm) lesions. Thus, prolonged cortical stimulation is a strategy to enhance motor recovery in photothrombotic infarct model rats. However, pattern and duration of stimulation requires modification depending on the extent of infarct.

Samul extract protects against the H2O2-induced apoptosis of H9c2 cardiomyoblasts via activation of extracellular regulated kinases (Erk) 1/2.

Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of ischemic heart and brain damages in Oriental medicine. However, little is known about the mechanism by which Samul rescues cells from cytotoxic damage. This study was designed to investigate the protective mechanisms of Samul on H(2)O(2)-induced death of H9c2 cells. Treatment with H(2)O(2) markedly decreased the viability of H9c2 cells in a dose- and time-dependent manner, which was significantly prevented by pre-treatment with Samul. The nature of death of H9c2 cells by H(2)O(2) was demonstrated by apoptotic features, including ladder-pattern fragmentation of genomic DNA and chromatin condensation, which were markedly abolished by pretreatment of Samul in H(2)O(2)-treated cells. We further demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the protective effects of Samul against H(2)O(2), whereas inhibitors of Jnk and p38 did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in H(2)O(2)-treated cells. In addition, treatment with Samul also resulted in an increase of expression of anti-apotogenic Bcl2 protein, which was decreased by H(2)O(2). However, it inhibited the expression of apotogenic Bax protein in H(2)O(2)-treated cells. Taken together, these results suggest that the protective effects of Samul against oxidative damage may be achieved via activation of MAP kinase, Erk as well as Bcl2 family proteins.

Sasim attenuates LPS-induced TNF-α production through the induction of HO-1 in THP-1 differentiated macrophage-like cells

AIM OF THE STUDY Sasim, a traditional prescription composed of seven herbal mixtures, has been widely used as an oriental medicine for the treatment of cerebral infarction in Korea. However, the regulatory mechanisms by which the formula affects immune processing in cerebral infarction patients remain unknown. MATERIALS AND METHODS The levels of secretory protein of tumor necrosis factor (TNF)-alpha were determined in both THP-1 differentiated macrophage-like (THP-1/M) cells and Peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. Also, the levels of protein and mRNA of TNF-alpha and heme oxygenase-1 (HO-1) were detected in THP-1/M cells under our experimental condition. RESULTS Sasim markedly suppressed lipopolysaccharide (LPS)-induced TNF-alpha at the levels of secretory protein and mRNA in both PBMCs from cerebral infarction patients and THP-1/M cells. Interestingly, Sasim strongly induced HO-1, the rate-limiting enzyme of heme catabolism, at both the protein and mRNA levels in THP-1/M cells. Treatment with tin protoporphyrin IX (SnPP), an inhibitor of the catalytic activity of HO, significantly abolished the suppressive effect of Sasim on LPS-induced TNF-a production in THP-1/M cells. CONCLUSIONS These data indicate that Sasim may be beneficial in the cessation of inflammatory processes associated with cerebral infarction through the induction of HO-1 expression.

Dual extradural cortical stimulation in chronic stroke patients with large infarcts: technical case report

Abstract Objective and importance: Recent works on extradural cortical stimulation have been successful in improving neurological recovery in chronic stroke patients. On the other hand, single perirolandic stimulations are often associated with disappointing results. Clinical presentation: We report two cases of chronic stroke in which the magnitude of infarct was too large to be improved with single perirolandic stimulation. Patient 1 had severe hemiplegia associated with large cortical infarct in the right frontoparietal area. The patient could neither stand independently or walk. Patient 2 had hemiplegia and aphasia due to cortical infarct in the left middle cerebral artery territory. Both patients had intensive rehabilitative training for more than 6 months with no beneficial results. Intervention: Two paddle electrodes covering frontal and parietal area were implanted, followed by dual cortical stimulation with concurrent rehabilitative training in patient 1. After 6 months of stimulation, the patient could walk with a good posture. Two paddle electrodes were implanted to cover pre-motor and motor cortex in patient 2. After similar treatment, the motor function was markedly improved. Conclusion: Dual cortex stimulation, which acts on more diffuse areas or functionally related areas, is beneficial to promote the motor recovery in chronic stroke patients with large infarcts.