Hak Cheol Kwon

Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid β-protein via the PI3K/Akt/Bad/BclXL-regulated mitochondrial apoptotic pathway

Amyloid β-protein (Aβ), which is deposited in neurons as neurofibrillary tangles, is known to exert cytotoxic effects by inducing mitochondrial dysfunction. Additionally, the PI3K/Akt-mediated interaction between Bad and Bcl(XL) plays an important role in maintaining mitochondrial integrity. However, the application of therapeutic drugs, especially natural products in Alzheimers disease therapy via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway has not aroused extensive attention. In the present study, we investigated the neuroprotective effects of hyperoside, a bioactive flavonoid compound from Hypericum perforatum, on Aβ(25-35)-induced primary cultured cortical neurons, and also examined the potential cellular signaling mechanism for Aβ detoxication. Our results showed that treatment with hyperoside significantly inhibited Aβ(25-35)-induced cytotoxicity and apoptosis by reversing Aβ-induced mitochondrial dysfunction, including mitochondrial membrane potential decrease, reactive oxygen species production, and mitochondrial release of cytochrome c. Further study indicated that hyperoside can activate the PI3K/Akt signaling pathway, resulting in inhibition of the interaction between Bad and Bcl(XL), without effects on the interaction between Bad and Bcl-2. Furthermore, hyperoside inhibited mitochondria-dependent downstream caspase-mediated apoptotic pathway, such as that involving caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP). These results demonstrate that hyperoside can protect Aβ-induced primary cultured cortical neurons via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway, and they raise the possibility that hyperoside could be developed into a clinically valuable treatment for Alzheimers disease and other neuronal degenerative diseases associated with mitochondrial dysfunction.

Tripartin, a Histone Demethylase Inhibitor from a Bacterium Associated with a Dung Beetle Larva

Tripartin (1), a new dichlorinated indanone, was isolated from the culture broth of the Streptomyces sp. associated with a larva of the dung beetle Copris tripartitus Waterhouse. The planar structure of tripartin (1) was identified by the spectroscopic analyses of NMR, mass, UV, and IR data. The structure was confirmed, and the absolute configuration of 1 was determined by X-ray crystallography. Tripartin displayed specific activity as an inhibitor of the histone H3 lysine 9 demethylase KDM4 in HeLa cells.

Apoptosis-inducing effect of diketopiperazine disulfides produced by Aspergillus sp. KMD 901 isolated from marine sediment on HCT116 colon cancer cell lines.

Aims:  Research is to identify the bioactive secondary metabolites produced by Aspergillus sp. KMD 901 isolated from marine sediment and to assess their apoptosis‐inducing effects.

KG-135, enriched with selected ginsenosides, inhibits the proliferation of human prostate cancer cells in culture and inhibits xenograft growth in athymic mice.

Sun ginseng (SG) was recently developed as a heat-processed form of ginseng. The Rg3, Rk1, and Rg5 ginsenosides are its main ginsenoside components. SG has been reported to have more potent pharmacological activities than red ginseng (RG), where these pharmacological activities include vasodilatory, anti-oxidant and anti-tumorigenic effects. In the present study, we investigated KG-135, the ginsenoside-rich fraction of SG and demonstrated that this fraction inhibits proliferation of human prostate cancer cells both in vitro and in vivo. KG-135 caused a significant growth inhibition of DU145 and PC-3 human prostate cancer cells. KG-135 induced cell cycle arrest in the G1 phase and caused an associated increase in the p21(Cip1) protein levels. When KG-135 was fed to mice that had been xenografted with DU145 tumors, a time-dependent inhibition of tumor growth was noted without any observed toxicity. Immunohistochemical analysis of the tumor tissues showed that KG-135 led to a decrease in the expression of proliferating cell nuclear antigen (PCNA). Microarray analysis of the tumors revealed that KG-135 inhibited tumor growth and also caused changes in the expression levels of multiple cancer-related genes. These data suggest that KG-135 effectively inhibits prostate cancer cell proliferation. Its mechanism of action likely involves cyclin inhibition and regulation of the expression of the TNFRSF25 and ADRA2A genes.

Sargahydroquinoic acid inhibits TNFα-induced AP-1 and NF-κB signaling in HaCaT cells through PPARα activation.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, their ligands are targets for the treatment of various skin disorders, such as photo-aging and chronological aging of skin. Intensive studies have revealed that PPARα/γ functions in photo-aging and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). However, the detailed mechanism of PPARα/γs role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARα/γ ligand significantly decreased Tumor Necrosis Factor-alpha (TNFα)-induced MMP-2/-9 expression by downregulating TNFα-induced transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARα antagonist) not bisphenol A diglycidyl ether (PPARγ antagonists), reversed the effect on TNFα-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFα-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-κB pathway via PPARα.

Colwellia asteriadis sp. nov., a marine bacterium isolated from the starfish Asterias amurensis

A marine bacterial strain, KMD 002T, was isolated from an Amur starfish, Asterias amurensis, collected in the East Sea of Korea. Strain KMD 002T was a Gram-negative, beige-pigmented, rod-shaped bacterium. The strain was capable of growth at relatively low temperatures (4-25 degrees C) and over a broad pH range (pH 4.0-10.0). The major fatty acids were C16:1omega7c and/or iso-C15:0 2-OH and C16:0 and the predominant isoprenoid quinone was Q-8. The DNA G+C content of strain KMD 002T was 40.3 mol%. Phylogenetic analysis using 16S rRNA gene sequences revealed that strain KMD 002T belonged to the genus Colwellia. However, various phenotypic properties as well as low 16S rRNA gene sequence similarities to members of the genus Colwellia (94.1-96.7%) suggested that strain KMD 002T is a representative of a novel species, for which the name Colwellia asteriadis sp. nov. is proposed. The type strain is KMD 002T (=KCCM 90077T =JCM 15608T).

Coprismycins A and B, neuroprotective phenylpyridines from the dung beetle-associated bacterium, Streptomyces sp.

Two new phenylpyridines, named coprismycins A and B (1 and 2), and previously reported dipyridines (3-6) were isolated from a culture of Streptomyces sp. associated with the dung beetle, Copris tripartitus. The structures of the coprismycins (1 and 2) were elucidated by the analysis of 1D and 2D NMR spectra and mass, UV, and IR spectra. Coprismycins A-B (1 and 2) and dipyridines (5 and 6) displayed comparable neuroprotective effects against MPP(+) (1-methyl-4-phenylpyrimidium)-induced neurotoxicity in neuroblastoma SH-SY5Y cells.

Kistimonas asteriae gen. nov., sp. nov., a gammaproteobacterium isolated from Asterias amurensis

A novel marine bacterium, strain KMD 001(T), was isolated from the starfish Asterias amurensis, which inhabits the East Sea of Korea. Strain KMD 001(T) was aerobic, light-yellow pigmented and Gram-stain-negative. Analyses of the 16S rRNA gene sequence revealed that strain KMD 001(T) represents a novel lineage within the class Gammaproteobacteria. Strain KMD 001(T) is closely related to the genera Endozoicomonas and Zooshikella, which belong to the family Hahellaceae and to the order Oceanospirillales. The 16S rRNA gene sequence of strain KMD 001(T) shows similarities of approximately 91.8-94.6 % with the above-mentioned genera. The DNA G+C content of KMD 001(T) is 47.6 mol%. It contains Q-9 as the major isoprenoid quinone. The predominant fatty acids were determined to be anteiso-C(15 : 0), iso-C(15 : 0), iso-C(14 : 0) and iso-C(16 : 0). Strain KMD 001(T) should be assigned to a novel bacterial genus within the class Gammaproteobacteria based on its phylogenetic, chemotaxonomic and phenotypic characteristics. The name Kistimonas asteriae gen. nov., sp. nov. is proposed. The type strain is KMD 001(T) (=KCCM 90076(T) =JCM 15607(T)).

A new phenolic amide from the roots of Paris verticillata.

A new phenolic amide 8, together with the nine known phenolic compounds 1-7, 9 and 10 were isolated from the MeOH extract of the roots of Paris verticillata. The structure of the new compound 8 was determined to be 1-N-feruloylaminobutyl-4-ρ-hydroxybenzamide by spectroscopic methods. The isolated compounds were tested for cytotoxicity against four human tumor cell lines using the SRB assay.

Aeromicrobium halocynthiae sp. nov., a taurocholic acid-producing bacterium isolated from the marine ascidian Halocynthia roretzi.

A marine bacterium, strain KME 001(T), was isolated from the siphon tissue of a marine ascidian, Halocynthia roretzi, collected off the coast of Gangneung, Korea. Strain KME 001(T) was a Gram-positive, aerobic, non-spore-forming, rod-shaped and non-motile bacterium. Phylogenetic analysis using 16S rRNA gene sequences revealed that strain KME 001(T) clustered with the genus Aeromicrobium and was closely related to Aeromicrobium ginsengisoli, Aeromicrobium erythreum and Aeromicrobium ponti with 97.7, 97.6 and 97.5 % sequence similarities, respectively. The strain was capable of growth at a variety of temperatures (10-42°C) and over a broad pH range (5.0-10.0). NaCl was required for robust growth of the strain. The diagnostic diamino acid of the cell-wall peptidoglycan was ll-diaminopimelic acid. The predominant menaquinone was MK-9(H(4)). The predominant fatty acids were C(18 : 1)ω9c, C(16 : 0) and 10-methyl C(18 : 0). The DNA-DNA hybridization analyses showed that DNA-DNA relatedness values between strain KME 001(T) and its nearest neighbours, A. ginsengisoli KCTC 19207(T), A. erythreum KCCM 41104(T) and A. ponti KACC 20565(T), were 49.6, 57.1 and 63.5 %, respectively. The DNA G+C content of strain KME 001(T) was 75.9mol%. Chemical investigation of the liquid culture medium of strain KME 001(T) led to the isolation of taurocholic acid as a major secondary metabolite. On the basis of phylogenetic and phenotypic data, strain KME 001(T) is classified as representing a novel species of the genus Aeromicrobium, for which the name Aeromicrobium halocynthiae sp. nov. is proposed. The type strain is KME 001(T) (=JCM 15749(T)=KCCM 90079(T)).