Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is characterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6- OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDAmediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion.

We investigated the potential of fucoidan for its ability to provide protection from gamma ray-induced damage. In our results, the fucoidan significantly improved the counts of endogenous colony forming unit to 9.5±1.5, from 5.5±2.5 compared with un-treated irradiated control group at 10 day after 7 Gy whole body irradiation. After 2 Gy irradiation, fucoidan treatment attenuated the percent of tail DNA of splenocytes, parameters of DNA damage, from 30.17±1.7% to 13.67±2.81% by comet assay and also accelerated the proliferation of splenocytes, compared with un-treated irradiated control group by ³H-thymidine incorporation assay. Furthermore, fucoidan decreased the number of apoptotic fragments per intestinal crypt by 31.8% at 1 days after 2 Gy irradiation. These results indicated that the fucoidan significantly improved the hematopoietic recovery, prevented the DNA damage in immune cells and enhanced their proliferation, which had been suppressed by ionizing radiation. in addition, fucoidan rescued intestinal cells from radiation-induced apoptosis. Thus, this study raises the possibility of using fucoidan as adjuvant therapeutic agent after radiotherapy.

The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours.

Parkinson is disease is known to exhibit progressive degeneration of the dopaminergic neurons in the substantia nigra via inhibition of glutathione metabolism. It is well known that 6-Hydroxydopamine (6-OHDA) induces Parkinson is disease-like symptoms, while resveratrol (3,5,4-trihydroxystilbene) has been shown to have anti-inflammatory and antioxidant effects. In the present study, we investigated the neuroprotective effects of resveratrol, a phytoalexin found in grapes and various plants, on 6-OHDA-induced cell damage to the SH-SY5Y human neuroblastoma cell line. Resveratrol (5 and 10§­) inhibited 6-OHDA (60 §­)-induced cytotoxicity in SH-SY5Y cells and induced a reduction of the number of apoptotic nuclei caused by 6-OHDA treatment. Additionally, the total apoptotic rate of cells treated with both resveratrol (10 §­) and 6-OHDA (60§­) was less than that of 6-OHDA treated cells. Resveratrol also dose-dependently (1, 5 and 10 §­) scavenged reactive oxygen species (ROS) induced by 6-OHDA in SH-SY5Y cells and prevented depletion of glutathione in response to the 6-OHDA-induced cytotoxicity in the glutathione assay. Overall, these results indicate that resveratrol exerts a neuroprotective effect against 6-OHDA-induced cytotoxicity of SH-SY5Y cells by scavenging ROS and preserving glutathione.

In this study, to understand the pathogenesis of new rabbit hemorrhagic disease virus (RHDVa) serotype, we carried out to administrate RHDVa to rabbits, and to examine sequential electron microscopic changes and relationship between pathogenesis and apoptosis. TUNEL-positive cells began to be observed from 24 hours after inoculation (HAI) and the number of positive cells was slightly increased with the course of time. Whereas marked increase of positive cells was seen in the liver from the rabbits died acutely. Typical viral particles with cup-like projections and a diameter of 30~40 nm were detected in homogenized liver samples and tissues at 36 and 48, and 48 HAI, respectively. Ultrastructurally, glycogen deposition was observed from the first stage of hepatocellular degeneration by RHDVa infection and then, swelling and disruption of cristae of mitochondria by viral particles, swelling of smooth endoplasmic reticulum, vacuoles and vesicles were detected. Condensation, margination and fragmentation of chromatin were observed in degenerative hepatocytes at 36 and 48 HAI, indicating apoptotic bodies. These data offer that hepatocytic apoptosis by RHDV infection could be closely related with mitochondrial impairment in the hepatocytes.

Ginsenoside Rp1 is one of ginseng saponins with chemotherapeutic activity. In this study, we investigated the effects of Rp1 on spleen cells. Spleen is a major immune organ consisted of crucial immune cells, such as T lymphocytes, B lymphocytes, natural killer cells, and some antigen-presenting cells. Although the anti-tumor potential of Rp1 was studied, the effects of Rp1 on immune cells have not investigated yet. A viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT), flow cytometric analysis, Western blot analysis were used to detect cellular changes on Rp1-treated spleen cells. MTT assay showed that Rp1 decreased the viability of spleen cells. To further investigate the effects of Rp1 on activated spleen cells, we treated lipopolysaccharide (LPS) as a representative inflammatory agent and Rp1 on spleen cells in a combination. The surface expression levels of activation markers for lymphocytes, CD25 and CD69 were measured. Apoptotic analysis revealed the cytotoxic effects of Rp1 on both na?e and activated cells, and the expression pattern of some apoptosis-related proteins was correlated to apoptotic events of cells. Taken together, ginsenoside Rp1 increases the cellular death of spleen cells and also inhibits the LPS-induced activation of spleen cells.

Classical swine fever (CSF) is a highly contagious disease among swine that has an important economic impact on worldwide. One clinical symptom of CSF is leukopenia, in particular lymphopenia, which is a characteristic event that occurs early in the course of CSF. Though lymphopenia associated with apoptosis, the pathogenic mechanism underlying the lymphopenia has not been well studied. To understand these mechanisms, we investigated the response of porcine B cell lines to infection with SW03, virulent strain isolated from swine tissue in Korea. This study demonstrated that SW03-infected L35 cell were induced apoptosis through the detection of activated caspase-3. In addition, SW03 infection leaded to alterations in pro-apoptotic, Bax, and anti-apoptotic, Bcl-xL proteins of Bcl-2 family. Our results would suggest that SW03-infected L35 cells induced apoptosis via intrinsic mitochondrial pathway.

In the present study, we expected the anti-tumor effect by combined treatment of arsenic trioxide and interferon (IFN)-α on murine Lewis lung carcinoma (LL2) cells through in vivo study. As a experimental model, LL2 cells (1×10∨6/mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached 100 ㎣, mice were treated with 1 mg/kg arsenic trioxide, 50000 IU IFN-α, or arsenic trioxide and IFN-α. The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN-α. In arsenic trioxide and IFN-α treated group, apoptotic index was reached a peak valve at 48 hr after the treatment and it was restored to approximately the control level at 8 days.

The irradiation of radioactive γ-ray induces apoptosis of radiosensitive organs for homeostasis. In this study, we investigated the repair mechanisms for homeostasis in the small intestine after cell damage by ∨60Co γ-ray irradiation. The apoptosis was most frequently observed in the crypt cells of the small intestine after four and six hours by radioactive γ-ray irradiation, and the frequency of apoptosis was proportional to the amount of irradiation. Also, the number of apototic cells was coincident with expression pattern of p53.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and potent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growth in vivo without detectable cytotoxic side effects. Interferon (IFN)-γ often modulates the anti-cancer activities of TNF family members including TRAIL. We previously reported that IFN-γ enhanced TRAIL-induced Apoptosis in HeLa cells without the unknown mechanism. In this study, we investigated whether IRF-1 involves in IFN-γ-enhanced TRAIL-induced apoptosis. We exposed HeLa cells to IFN-γ for 12 hours and then treated with recombinant TRAIL protein.