Jungsik Cho

Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice

To investigate whether selenium (Sel) treatment would impact on the onset of diabetes, we examined serum biochemical components including glucose and insulin, endoplasmic reticulum (ER) stress and insulin signalling proteins, hepatic C/EBP-homologous protein (CHOP) expression and DNA fragmentation in diabetic and non-diabetic conditions of non-obese diabetic (NOD) mice. We conclude that (i) Sel treatment induced insulin-like effects in lowering serum glucose level in Sel-treated NOD mice, (ii) Sel-treated mice had significantly decreased serum biochemical components associated with liver damage and lipid metabolism, (iii) Sel treatment led to the activation of the ER stress signal through the phosphorylation of JNK and eIF2 protein and insulin signal mechanisms through the phosphorylation of Akt and PI3 kinase, and (iv) Sel-treated mice were significantly relieved apoptosis of liver tissues indicated by DNA fragmentation assay in the diabetic NOD group. These results suggest that Sel compounds not only serve as insulin-like molecules for the downregulation of glucose level and the incidence of liver damage, but may also have the potential for the development of new drugs for the relief of diabetes by activating the ER stress and insulin signalling pathways.

Effects of age and strain on small intestinal and hepatic antioxidant defense enzymes in Wistar and Fisher 344 rats

Age- and strain-associated alterations in intestinal and hepatic antioxidant defense enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST), and lipid peroxidation were examined in Wistar and F344 rats of both strains aged 2 weeks, 2.5, 10 and 23 months. In the small intestine, activities of SOD and GSH-PX and lipid peroxidation were not affected by age or strain difference. Intestinal GST activity was noticeably increased with age in both strains, but somewhat different pattern of age-related changes occurred between two strains. Wistar rats aged 23 months had a significantly higher intestinal GST activity than corresponding age of F344 rats. In the liver, cytosolic SOD activity was not affected by age and strain, whereas GSH-PX and GST activities and lipid peroxidation were markedly influenced by age or strain difference. In particular, hepatic GSH-PX in Wistar rats resulted in a significant increase after 10 months of age and stayed at this level till 23 months of age we examined. Also, Wistar rats showed a higher lipid peroxidation in the liver of 2.5 months old when compared with corresponding age of F344 rats. However, F344 rats did not show any significant age-dependent changes in GSH-PX and lipid peroxidation. In contrast, the GST activity did show much of an age-associated alteration in both strains. Age-associated change in GST activity of Wistar rats was much greater than that observed in F344 rats, especially late in the lifetime (23 months old). It is concluded from our results that age has profound impact on development of some antioxidant enzymes in the small intestine and liver and also strain-related difference in development of antioxidant defense system was observed at least some time of rat life.

Animal Model for Alzheimer's Disease by PS2 Gene Transfer

Alzheimer’s disease (AD), the most common cause of dementia occurring in elderly humans, affected 8.3% people over 65 years of age in 1995, and during the next 20 years, the number of persons with AD will exceed 0.62 million in Korea. AD occurs when neurons in the memory and cognition regions of the brain are damaged and ultimately killed. A key step in this process is the polymerization of the Aβ-peptide into neurotoxic protein filaments. These filaments are accumulated in the cerebral cortex and hippocampus of AD patients as the extracellular senile plaques that are composed of the 40 to 42/3 amino-acid long peptide derived from the amyloid precusor protein (APP) and intracellular neurofibrillary tangles that are composed of twisted filament of tau protein. The PS2 gene accounts for about half of all cases of the early onset of AD, leading to the development of AD in patients younger than 60 years. Transgenic mice provide an important advance in the study of how the gene is associated with the human cognitive dysfunction after synaptic transmission between neurons in the brain. To generate transgenic mice, a hybrid gene containing human PS2 mutant (N141I) coding sequence and tet P consisting of seven copies of the tet O sequence were constructed. Separately, we also prepared another hybrid gene (pTet-tTAk) that carries the Tet-regulated promoter and tTAk coding sequence to generate double transgenic mice by mating with pTet-PS2 mutant transgenic mice. Prior to microinjection, both of the hybrid genes were tested in vitro to see whether Aβ-peptides are deposited in transfectant SK-N-MC neuroblastoma cells, and whether TA regulators are induced by tetracycline release in their transfectant cells in a dose-dependent manner. These two hybrid genes were then microinjected into fertilized mouse embryos for study of the in vivo function of the PS2 gene using transgenic mice. Our primary results showed that (1) the level of Aβ-peptides was increased in the PS2-transfectant cell; (2) expression of the TA genes was enhanced by the release of tetracyline in their TA-transfectants; (3) a total of 11 newborn mice were produced, one of which is identified as a transgenic mouse carrying pNSEPS2m; and (4) out of 36 founder mice, 7 transgenic mice carrying pTet-tTAk were confirmed by PCR analysis.