Yun-Young Kim

Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats

The mother-infant relationship is an instinctive phenomenon, and loss of maternal care in early life influences neonatal development, behavior and physiologic responses.1,2 Furthermore, the early loss may affect the vulnerability of the infant to neuropsychiatric disorders, such as childhood anxiety disorders, personality disorders and depression, over its lifespan.3,4 Fluoxetine is prescribed worldwide for depression and is often used in the treatment of childhood mental problems related to maternal separation or loss of maternal care.5,6 In the present study, fluoxetine was administrated to rats with maternal separation to determine its effects on neuronal development, in particular with respect to cell proliferation and apoptosis in the dentate gyrus of the hippocampus. Rat pups were separated from their mothers and socially isolated on postnatal day 14 and were treated with fluoxetine (5 mg kg−1) and 5-bromo-2′-deoxyuridine (BrdU) (50 mg kg−1) for 7 days, after which immunohistochemistry and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were carried out. In the pups with maternal separation treated with fluoxetine, the number of BrdU-positive cells was significantly increased and that of TUNEL-positive cells was significantly decreased in the dentate gyrus compared to pups with maternal separation that did not receive fluoxetine treatment. These findings indicate that fluoxetine affects new cell proliferation and apoptosis, and we propose that fluoxetine may be useful in the treatment of maternal separation-related diseases.

Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients

The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. We tested the genetic association between schizophrenia and lung cancer by analyzing polymorphic sites in the p53 gene. Genotype and allele frequencies at two polymorphic sites in the p53 gene (BstUI and MspI restriction sites in exon 4 and intron 6, respectively) were studied in Korean schizophrenia (n=179) and lung cancer patients (n=104). Comparisons of the genotype and allele frequencies of the MspI polymorphism revealed significant differences between schizophrenia and lung cancer patients. The results suggest that the p53 polymorphism specifically found in schizophrenia patients may be associated with reduced vulnerability to lung cancer.

Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas

Glioma tumour‐suppressor candidate region gene 2 (GLTSCR2/PICT‐1) is localized within the well‐known 1.4 Mb tumour‐suppressive region of chromosome 19q, which is frequently altered in various human tumours, including diffuse gliomas. Aside from its chromosomal localization, several lines of evidence, including PTEN‐phosphorylating and cell‐killing activities, suggests that GLTSCR2 participates in the suppression of tumour growth and development. However, little is known about the biological functions and molecular mechanisms of GLTSCR2 as a tumour suppressor gene. We investigated the pathological significance of GLTSCR2 expression in association with the development and progression of glioblastomas, the most common malignant brain tumour. We used real‐time PCR and western blot analysis to examine the expression levels of GLTSCR2 mRNA and protein in glioblastomas, normal brain tissue and in non‐glial tumour tissue of different origin, and found that GLTSCR2 expression is down‐regulated in glioblastomas. In addition, direct sequencing analysis and fluorescence in situ hybridization clearly demonstrates the presence of genetic alterations, such as a nonsense mutation and deletion, in the GLTSCR2 gene in glioblastomas. Finally, our immunohistochemical study demonstrates that GLTSCR2 is sequentially down‐regulated according to the histological malignant progression of the astrocytic glial tumour. Taken together, our results suggest that GLTSCR2 is involved in astrocytic glioma progression. Copyright

Cloning and characterization of pathogenesis-related protein 4 gene from Panax ginseng

The family of pathogenesis-related protein 4 (PR4) is a group of proteins with a Barwin domain in C-terminus and generally thought to be involved in plant defense responses. In the present study, PR4 (designated as PgPR4) cDNA was isolated from the leaf of Panax ginseng C.A. Meyer. and characterized. The ORF is 513 bp with a deduced amino acid sequence of 170 residues. A GenBank BlastX search revealed that the deduced amino acid of PgPR4 shares the highest sequence similarity to PR4 of Sambucus nigra (72% identity). Sequence and structural analysis indicated that PgPR4 belongs to class II of PR4 proteins. This is the first report on the isolation of PR4 gene from the P. ginseng genome. The high-level expression of PgPR4 was observed in the root as revealed by quantitative real-time PCR. The temporal expression analysis demonstrated that PgPR4 expression could be up-regulated by pathogen infection, salt, wounding, and hormone stresses. These results suggest that PgPR4 could play a role in the molecular defense response of ginseng to abiotic stress and pathogen attack.

Molecular characterization of MYB transcription factor genes from Panax ginseng

Transcription factors (TFs) are essential for gene regulation in all living organisms, including plants, where among numerous other functions, they control temporal and spatial gene expression in response to environmental stimuli. The v-myb avian myeloblastosis viral oncogene homolog (MYB) family is the largest TF family in plants, with its members involved in developmental processes as well as secondary metabolism. Little is known about MYB genes in Panax ginseng Meyer, despite ginseng’s importance as a widely-used medicinal plant. In this study, we isolated nine MYB genes from P. ginseng (PgMYBs). Phylogenetic comparison of these genes with the MYB genes of other plant species revealed that the PgMYBs clustered into different families based on their putative functions including terpene regulation; five PgMYBs clustered in the R2R3 family, and four PgMYBs clustered in the MYB-related protein group. Further expression analysis of five PgMYBs showed consistently high expression in flower and leaf tissue, suggesting that these PgMYB genes may be involved in development of the above-mentioned tissues. Four PgMYBs were downregulated in response to methyl jasmonate (MJ) and salicylic acid (SA), whereas PgMYB3 was up-regulated, suggesting a role for all these genes in stress response. This is the first comprehensive study of the MYB gene family in P. ginseng, and the information provided here will facilitate further exploration of the functions of these TFs.

Molecular characterization and expression analysis of pathogenesis related protein 6 from Panax ginseng

Panax ginseng Meyer is one of the important medicinal plants in the world, particularly in Asian countries. Ginseng encounters many stress exposure during its long cultivation period. However, the molecular mechanism of stress resistance is still poorly understood in spite of its importance. In this study, pathogenesis-related protein 6 (PR6), also called proteinase inhibitor (PI), was isolated from ginseng embryogenic callus, named PgPR6. The small size of PR6, containing an open reading frame of 219 bp encoding 72 amino acids, the typical characteristic of PR6 protein, shares the highest sequence similarity to PR6 of Theobroma cacao (69% identity). Sequence and structural analysis indicated that PgPR6 belongs to class Kunitz-type PI family. This is the first report pertaining to the identification of PR6 gene from the P. ginseng genome. The high-level expression of PgPR6 was observed in root as revealed by quantitative real-time PCR. The temporal expression analysis demonstrated that PgPR6 expression was highly up-regulated by signaling molecules, heavy metals, mechanical wounding, chilling, salt, sucrose, and mannitol stress, indicating that PgPR6 may play an important role in the molecular defense response of ginseng to a various range of environmental stresses.