An integrated analysis of microRNA and mRNA expression in salvianolic acid B-treated human umbilical vein endothelial cells

Yang, Hana,Lee, Seung Eun,Kim, Gun-Dong,Park, Cheung-Seog,Jin, Young-Ho,Park, Yong Seek 대한독성유전단백체학회 2013 Molecular & cellular toxicology Vol.9 No.1

MicroRNAs (miRNAs) are a class of small noncoding RNAs, producing transcripts of about 22 nucleotides in length. miRNAs usually function as antisense regulators of other RNAs by degrading their targets. Recently, miRNAs have emerged as interesting new drug targets due to their regulatory role in essential biological processes. Salvianolic acid B (SalB) is one of the major pharmacologically active ingredients of Salvia miltiorrhiza, a traditional oriental medicine for treatment of cardiovascular disorders. In this study, we determined whether miRNAs play a role in regulation of various gene expression responses to SalB in human umbilical vein endothelial cells (HUVECs). We used the microarray approach to evaluate levels of both miRNA and mRNA, and found that 171 miRNAs were differentially expressed in SalB-treated HUVECs. We additionally identified 848 messenger RNAs (mRNAs) that are anti-correlated with the miRNAs expression. The Gene Ontology (GO) term enrichment was analyzed for identification of biological processes of target genes affected by differential expression of miRNA. Among 848 genes investigated, cardiovascular disease-related genes were selected in SalB-treated HUVECs. These results suggest that SalB may modulate miRNA and their target gene expression in order to exert vascular protective effects in human endothelial cells.

Immobilization of para-nitrobenzyl esterase-CLEA on electrospun polymer nanofibers for potential use in the synthesis of cephalosporin-derived antibiotics

Sekhon, Simranjeet Singh,Park, Jae-Min,Ahn, Ji-Young,Park, Tae Sun,Kwon, Soon-Dong,Kim, Yoon-Chul,Min, Jiho,Kim, Yang-Hoon 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.10 No.2

The para-nitrobenzyl esterase (PNBE) was successfully immobilized onto electrospun polystyrene/poly(styrene-co-maleic anhydride) (PS/PSMA) nanofibers as cross-linked enzyme aggregates (CLEA). The maximum amount of PNBE immobilized on the PS-PSMA nanofibers was determined to be 56.4 mg/g of nanofibers. The variation of pH and temperature has been observed to affect the enzymatic activity of the free and immobilized PNBE-CLEA. The immobilized PNBE-CLEA has been observed to show improved stability as compared to the native one. PNBE-CLEA has been found to retain more than 63% activity after 60 consecutive reuses. Finally, the immobilized PNBE-CLEA presented a high decomposition efficiency of cephalexin tosylate PNB ester. The durability determination of PNBE-CLEA immobilized nanofibers showed 70% of de-esterification after 10 cycles. These results demonstrate that PNBE-CLEA immobilized nanofiber could be used as an economical and environment friendly system for the catalytic process of para-nitrobenzyl esters in pharmaceutical synthesis.

Advances in antimicrobial agents based lysosomes

Bang, Seung Hyuck,Sekhon, Simranjeet Singh,Ahn, Ji-Young,Kim, Yang-Hoon,Min, Jiho 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.10 No.3

The emergence of drug resistance in common bacteria and the rapid emergence of new infections have motivated the need for the development of eco-friendly agents that do not contain any organic or inorganic material. The development of therapeutic agents which are able to remove or treat bacteria and cancer cell is very important and it should be very rapid, cost effective and nontoxic. Lysosomes are important against all other subcellular constituents due to their polymorphism as well as their involvement in both physiological and pathological processes. Lysosomes, which generally contain 50-60 hydrolases that constitute the cellular site for bulk macromolecule degradation, function to mediate several processes in the cell. They are single membrane bound cytoplasmic organelles involved in the degradation of intracellular protein. Lysosomal enzymes in lysosomes can be used as endocytosis for inhibiting bacteria phagocytosis as well as in antimicrobial activity. Many attempts have been made to increase the lysosomal activity by using different sources and significant changes have been observed in lysosome activity under starvation condition of reduced glucose. The treatment of some of the reagents and optimized aging cell with cell passage has also been used to evaluate an increase in their antimicrobial activity. The antimicrobial activity of lysosomes with various bacteria extracted from different sources has been observed. In the present review, the antimicrobial activity of lysosomes isolated from various sources such as human, bacteria and animals against different microorganisms has been discussed.

Effects of zinc oxide nanoparticles on gene expression profile in human keratinocytes

Lee, Seung Ho,Pie, Jae-Eun,Kim, Yu-Ri,Lee, Hee Ra,Son, Sang Wook,Kim, Meyoung-Kon 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.8 No.2

Zinc oxide (ZnO) nanoparticle is added in various materials and products such as paints, plastics, ceramics, glass, rubber, pigments and sunscreen. Especially, ZnO nanoparticles are widely used in UV protection, because of their property of absorption ultraviolet light. Despite the widespread use of ZnO nanoparticles, there are many unknowns in understanding on their nanotoxicity and mechanisms. In this study, we evaluated the effects of ZnO nanoparticles on gene expression pattern of human keratinocyte cells. Total RNA was prepared from the exposure groups to ZnO nanoparticles with different surface charge, and cDNA microarray was performed using Agilent human whole genome array. Our study indicated that genes related to apoptosis and response to stress including heme oxygenase 1 (HMOX1), superoxide dismutase (SOD), glutathione peroxidase (GPX), BNIP3L (adenovirus E1B 19 kDa interacting protein 3) and heat shock 70 kDa protein (HSP70) were up- and down-regulated in ZnO nanoparticles treated cells. Moreover, our results showed that ZnO nanoparticles induced intracellular reactive oxygen species (ROS) and oxidative stress. Antioxidant enzyme SOD levels were significantly higher and GSH levels were decreased in ZnO nanoparticles-exposed cells, respectively. The present study showed that up-regulation of these genes by ZnO nanoparticles could increase the production of ROS and oxidative stress. Therefore, ZnO nanoparticles could have a potential to product ROS through the perturbation of metabolic pathway, inducing oxidative stress. It also supported that the nanotoxicity mechanism could correlate with the active oxygen production, oxidative stress, apoptosis, and antioxidant defense mechanisms.

Genetic association of KCNA5 and KCNJ3 polymorphisms in Korean children with epilepsy

Choi, Byung Joon,Yoon, Jung Hwan,Choi, Won Seok,Kim, Olga,Nam, Suk Woo,Park, Won Sang 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.10 No.2

Shaker-like potassium channel and inward rectifying potassium channel are involved in spontaneity of seizure and pharmacoresistant seizure. Kv1.5 (KCNA5) is a Shaker subfamily channel gene. Mutations of Shaker subfamily channels lead to epilepsy. In addition, Kir3.1 inwardly rectifying channel (KCNJ3) is also one of the independent genes associated with seizure susceptibility. We investigated the allele and genotype frequencies of KCNA5 G182R and E211D polymorphisms and KCNJ3 T1505 polymorphism in 160 Korean pediatric epilepsy patients and 369 healthy Korean children. For the KCNA5 gene, the G182R and E211D polymorphisms showed only the C/C genotype in both healthy and epilepsy groups. For the KCNJ3 gene, the frequency of genotype A/A, A/T, and T/T was 142, 16, and 2 in epilepsy and 327, 42, and 0 in healthy individuals, respectively (P<0.05). Polymorphisms of the KCNA5 G182R and E211D and the KCNJ3 T1505 may not be associated with epilepsy in Koreans.

The role of antioxidant enzymes in adaptive responses to environmental toxicants in vascular disease

Lee, Seung Eun,Park, Yong Seek 대한독성유전단백체학회 2013 Molecular & cellular toxicology Vol.9 No.2

Human exposure to environmental toxicants is known to contribute to the development of vascular disease. Inhalation of environmental toxicants induces inflammation and oxidative stress in the vascular system and results in tissue damage, with subsequent impairment of the vascular system. The induction of antioxidant enzyme expression is one of the most crucial components of the cellular defense against environmental insults, and represents an adaptive response. The antioxidant enzyme-mediated adaptive response has been demonstrated to attenuate toxicity caused by oxidative stress as well as inflammation. Accumulating evidence indicates that antioxidant enzymes may protect against environmental toxicants. This review highlights the role of antioxidant enzymes in the adaptive response to environmental toxicants, and explores strategies for their clinical use.

Treatment with granulocyte colony-stimulating factor aggravates thrombocytopenia in irradiated mice

Son, Yeonghoon,Bae, Min Ji,Lee, Chang Geun,Jo, Wol Soon,Kim, Sung Dae,Yang, Kwangmo,Jang, Hyosun,Kim, Joong Sun 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol.9 No.3

Ionizing radiation can damage the hematopoietic system, and treatment with cytokines, including granulocytecolony-stimulating factor (G-CSF), is used to enhance hematopoietic recovery. In the present study, mice were whole-body irradiated with a sublethal dose of 5 Gy to produce severe myelosuppression and to evaluate the hematologic consequences of G-CSF treatment following irradiation. G-CSF ($100{\mu}g/kg$ of body weight) was injected immediately after irradiation, and then every three days for 3 weeks. G-CSF significantly ameliorated the decrease in peripheral neutrophils typically observed after exposure to radiation, but it also aggravated the decrease in the number of peripheral platelets during days 3-14 following irradiation. In the histological analysis, while the number of megakaryocytes was significantly decreased in the bone marrow, a number of trapped megakaryocytes were observed in the spleen of G-CSF-treated and irradiated mice. These data suggest that radiation-induced thrombocytopenia is worsened by G-CSF administration, possibly due to a decrease in the number of megakaryocytes in the bone marrow and an increase in the trapping of megakaryocytes in the spleen.

A safety assessment of phototoxicity and sensitization of $SiO_2$ nanoparticles

Choi, Jae-Eun,Park, Yoon-Hee,Lee, Eun-Young,Jeong, Sang-Hoon,Kim, Sun-Yae,Kim, Meyoung-Kon,Son, Sang-Wook 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.2

Despite widespread use of silicon dioxide ($SiO_2$) NPs in industry and in our daily lives, no studies so far have evaluated the potential of their skin phototoxicity and sensitization. This study was designed to investigate the potential of phototoxicity and sensitization of $SiO_2$ NPs. Assessment of the potential of skin phototoxicity was carried out using the 3T3 neutral red uptake test, an HSEM, and an animal model. The potential of skin sensitization was evaluated by a non-radioisotope local lymph node assay (non-RI LLNA). Findings from the present study suggest that the HSEM may be a reasonable model system for evaluation of skin phototoxicity of NPs. In addition, our data demonstrate that non-RI LLNA may be a useful method for identification of skin sensitization of NPs. In this study, we showed that $SiO_2$ NPs do not induce phototoxicity or skin sensitization.

Semantic networks for genome-wide CNV associated with AST and ALT in Korean cohorts

Kim, Hyo-Young,Park, Jun-Hyung,Kim, Heebal,Kang, Byeong-Chul 대한독성유전단백체학회 2013 Molecular & cellular toxicology Vol.9 No.2

Copy number variation (CNV) is an emerging approach to study about human health and diseases. Liver-related biochemical tests (aspartate aminotransferase: AST, alanine aminotransferase: ALT) are useful for diagnosing a patient with liver injury. We analyzed a CNV-based GWAS of AST and ALT in 407 Korean. Affymetrix Human 6.0 Array was used to identify CNV, and CNV segmentation was performed using CNV analysis software. Univariate linear regression was used for the GWAS using R package. We identified 64 CNVs associated with AST or ALT, and screened 228 genes located within our CNVs. In this study, we focused on semantic networks about liver disease using knowledge integration software. This semantic networks about liver disease contained entities like gene, disease, pathway, chemical, drug, and contained relationships between two entities like gene-pathway, gene-disease, pathway-chemical, disease-pathway, chemical-drug. Application of semantic networks shown three clusters, including four diseases (hepatocellular carcinoma, liver neoplasm, liver cell adenoma, drug-induced liver injury), one pathway (hepatitis C pathway), and seven drugs (acetaminophen, chlormezanone, stavudine, enflurane, isoniazid, mebendazole, nitisinone).

Comparison of gene expression changes induced by exposure to Ag, Cu-$TiO_2$, and $TiO_2$ nanoparticles in zebrafish embryos

Park, Hyung-Geun,Yeo, Min-Kyeong 대한독성유전단백체학회 2013 Molecular & cellular toxicology Vol.9 No.2

Nanomaterials composed of silver (Ag), copper-doped titanium dioxide (Cu-$TiO_2$), and pure titanium dioxide ($TiO_2$) have wide applications in consumer products such as cosmetics, electronic appliances, clothes, and industry materials such as solar cell. However, there are problems associated with the exposure of aquatic organisms in the ecosystem to such nanomaterials. In this study, we investigated the expression pattern of genes in zebrafish embryos after exposure to nanomaterials. We used several functional categories including apoptosis, endocytosis, immune response, and endoplasmic reticulum stress so on. A total of 314 (278 up-regulated and 36 down-regulated), 283 (129 up-regulated and 154 down-regulated), and 360 (198 up-regulated and 162 down-regulated) genes were differentially expressed in zebrafish embryos exposed to Ag, Cu-$TiO_2$, and $TiO_2$ NPs, respectively, with apoptosis being the function of the highest proportion of differentially expressed genes in all 3 NP exposures. Our data provide a basis for conducting further mechanistic studies of genes that are induced or suppressed upon exposure to NPs in zebrafish embryogenesis.