Alteration in miRNA Expression Profiling with Response to Nonylphenol in Human Cell Lines

Paul, Saswati,Kim, Seung-Jun,Park, Hye-Won,Lee, Seung-Yong,An, Yu-Ri,Oh, Moon-Ju,Jung, Jin-Wook,Hwang, Seung-Yong The Korean Society of Toxicogenomics and Toxicopro 2009 Molecular & cellular toxicology Vol.5 No.1

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

Paul, Saswati,Jeon, Won Kyung,Bizon, Jennifer L.,Han, Jung-Soo Frontiers Media S.A. 2015 FRONTIERS IN AGING NEUROSCIENCE Vol.7 No.-

<P>A substantial number of studies on basal forebrain (BF) cholinergic neurons (BFCN) have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD), and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA) axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine (ACh), glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, to which could help decipher disease states and propose leads for pharmacological intervention.</P>

Impact of miRNA deregulation on mRNA expression profiles in response to environmental toxicant, nonylphenol

Saswati Paul,김승준,박혜원,이승용,안유리,오문주,정진욱,류재천,황승용 대한독성 유전단백체 학회 2011 Molecular & cellular toxicology Vol.7 No.3

MicroRNA (miRNA) are approximately 22nt RNA molecules with the ability to regulate gene expression by interacting with its target mRNA. Recent studies demonstrated that miRNA are responsible for determining cell fate and also plays an important role in cellular response to xenobiotics stress and other toxicological phenomenon. Also a number of reports have strengthened the correlation between altered miRNA expression and various cancers. In this study miRNA and mRNA expression profiling was carried out in in-vitro differentiating MCF-7 and HepG2 cell line to understand the effect of nonylphenol (NP), an industrially synthesized environmental toxicant. Analyzing the mRNA- miRNA interaction, we observed correlation between deregulated miRNAs and its predictive differentially expressed target mRNA. We also observed differential expression of two widely studied miRNAs,miR-21 and miR-34 in these cell lines. CTCF is found to be the predictive target of expressed miR-21 in MCF-7. In HepG2 cell line expressed MDM2 is found to be a predictive target of miR-34b. These results support the possible role of miRNA interaction in the expression of its target genes and also ability of environmental toxicant to deregulate miRNA expression.

Multiple biological properties of macelignan and its pharmacological implications

Saswati Paul,황재관,김한영,Won Kyung Jeon,정지혜,한정수 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.3

Macelignan found in the nutmeg mace ofMyristica fragrans obtains increasing attention as a newavenue in treating various diseases. Macelignan has beenshown to possess a spectrum of pharmacological activities,including anti-bacterial, anti-inflammatory, anti-cancer,anti-diabetes, and hepatoprotective activities; recently, it hasalso been shown to have neuroprotective activities. Thisreview summarizes the current research on the biologicaleffects of macelignan derived from M. fragrans, withemphasis on the importance in understanding and treatingcomplex diseases such as cancer and Alzheimer’s disease.

Application of the Emerging Technologies in Toxicogenomics: An Overview

유소연,Saswati Paul,황승용 한국바이오칩학회 2016 BioChip Journal Vol.10 No.4

Toxicogenomics is a rapidly developing area of research which combines the understanding of molecular and cellular regulation in response to interaction of chemical stressors. Moreover, the emergence of comprehensive research method covering genomic, proteomic, and metabonomics analysis including bioinformatics has further substantiated the field of toxicogenomics. Thus, evaluation of such integrated analysis, conversing from variety of experimental techniques, along with the resulting database can decipher the importantance of such techniques in toxicogenomics. In addition, recent integration of epigenetic study (DNA Methylation, histone modification, small and noncoding RNAs) with toxicogenomics can pave the path to elucidate, highly reliable research results. The objective of the present review is to expand these understandings of toxicogenomics approach and validate the contribution of the developing research methods (genome, proteome, metabolites) to emphasize its importance in future toxicogenomics research.

Comparative Analysis of Gene Expression Patterns after Exposure to Nonylphenol in Human Cell Lines

오문주,Saswati Paul,김승준,김준섭,윤종필,박혜원,김연정,류재천,이철우,김현미,최경희,김학주,황승용 한국바이오칩학회 2008 BioChip Journal Vol.2 No.4

Nonylphenol (NP), a byproduct of industrial synthesis, is quite similar to estrogen in structure, and is known as an environmental estrogen that induces estrogenic disturbances. It has been utilized in several industries for the manufacture of skin cleaning materials, kitchen detergents, cosmetics, fabric detergents, and ink binder. Due to its characteristic strong estrogenic potency, NP is capable of disrupting the reproductive hormone system. Exposure to NP for a prolonged period increases the chances of developing breast and lung cancers. In this study, we conducted a comparative study of expression profiles between HK (Human Kidney cell), MCF-7 (Human breast cancer cell), and LNCaP (Human prostate cancer cell) cells treated with NP at the value of IC20, using Agilent whole genome microarrays. After comparative analysis, we detected some specific expression patterns in each of the cell lines. However, the expression patterns from the HK-2 and MCF-7 cells are quite similar. Interestingly, estrogen receptor 1 and 2 genes were downregulated only in MCF-7 cells, whereas the androgen receptor (AR) gene evidenced overexpression in all 3 of the cell lines. The PDZK1 gene, which has been identified as an estrogen-responsive gene, has also been shown to be overexpressed in all 3 of the tested cell lines. The majority of differentially expressed genes in NP treatment were shown to be involved in cell proliferation, transcription, and signaling. These results may establish a framework for nderstanding the mechanisms underlying the toxicity of NP.

Gene Expression Profiles of Nonylphenol as Representative EDCs in Normal Human Kidney HK-2 Cells

김승준,오문주,박혜원,김준섭,Saswati Paul,하정미,김연정,류재천,이철우,김현미,최경희,황승용 한국바이오칩학회 2008 BioChip Journal Vol.2 No.2

Nonylphenol (NP) is an organic compound of the wider family of alkylphenols and is a product of industrial synthesis formed during the alkylation process of phenols, particularly in the synthesis of polyethoxylate detergents. NP is an endocrine disruptors. Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the potential to hamper with hormonal regulations and the normal endocrine system and consequently cause health effects. In numerous chemical substances, the action mechanism of an endocrine disruptor is not clearly understood. In the present study, in vitro gene expression profiles were analyzed in nonylphenol-treated HK-2 cells using an Agilent Human 4×44 K whole genome array including 41,000 transcripts. Gene expression profiles were analyzed 3 and 48 hrs after exposure to NP with 2 different doses. We analyzed the gene expression profiles in order to understand the biological effects at level of gene functions and their time-dependent effects. A total of 1,727 genes were identified as being either over or down-expressed over 2-fold changes (P-value⁄0.05) in NP treated HK-2 cells. The functional classification of differentially expressed genes showed that cell death related genes were regulated by NP in HK-2 cells. 79 genes were time-dependent and differentially expressed, while 259 genes were concentration-dependent, all of which were selected using an ANOVA method. These data may support the understanding of the toxicity of nonylphenol in normal human kidney cells.

Induced Pluripotent Stem Cell Research: A Revolutionary Approach to Face the Challenges in Drug Screening

Minjung Song,조쌍구,Saswati Paul,임혜진,아브달아메드 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.2

Discovery of induced pluripotent stem (iPS) cells in 2006 provided a new path for cell transplantation and drug screening. The iPS cells are stem cells derived from somatic cells that have been genetically reprogrammed into a pluripotent state. Similar to embryonic stem (ES) cells, iPS cells are capable of differentiating into three germ layers, eliminating some of the hurdles in ES cell technology. Further progress and advances in iPS cell technology, from viral to non-viral systems and from integrating to non-integrating approaches of foreign genes into the host genome, have enhanced the existing technology, making it more feasible for clinical applications. In particular, advances in iPS cell technology should enable autologous transplantation and more efficient drug discovery. Cell transplantation may lead to improved treatments for various diseases, including neurological, endocrine, and hepatic diseases. In studies on drug discovery, iPS cells generated from patient-derived somatic cells could be differentiated into specific cells expressing specific phenotypes, which could then be used as disease models. Thus, iPS cells can be helpful in understanding the mechanisms of disease progression and in cell-based efficient drug screening. Here, we summarize the history and progress of iPS cell technology, provide support for the growing interest in iPS cell applications with emphasis on practical uses in cell-based drug screening, and discuss some challenges faced in the use of this technology.

Depressive-Like Behaviors in a Rat Model of Chronic Cerebral Hypoperfusion

Lee, Sang Rim,Choi, Boryoung,Paul, Saswati,Seo, Ju-Ha,Back, Dong Bin,Han, Jung-Soo,Choi, Dong-Hee,Kwon, Kyoung Ja,Shin, Chan Young,Lee, Jongmin,Han, Seol-Heui,Kim, Hahn Young Springer-Verlag 2015 Translational stroke research Vol.6 No.3

Gene Expression Patterns of Environmental Chemicals in Human Cell Lines using HazChem Human Array

박혜원,김승준,오문주,윤종필,하정미,Saswati Paul,김연정,류재천,황승용 한국바이오칩학회 2009 BioChip Journal Vol.3 No.1

The human HazChem array includes 16 control genes and 300 environmental toxicity-related genes. In past experiments, the expression levels of these genes were altered in whole genome microarray experiments using VOCs and PAH-treated human cells. In this study, we employed the human HazChem array to determine the gene expression pattern of chemical groups. The chemical groups used in this study were PAHs, POPs, and VOCs. PAHs are one of the most widespread organic pollutants. We used chrysene and phenanthrene as examples of PAHs. POPs are chemical substances that remain in the environment, and bioaccumulate through the food chain. We utilized chlordane and toxaphene as our sample POPs. VOCs are important outdoor air pollutants. They have been shown to cause nervous system disorders through respiration and skin contact, and generally are associated with foul odors. We utilized dichloromethane, ethylbenzene, and trichloroethylene as our sample VOCs. Thus, a total of 7 chemicals were assessed. In this study, HepG2 cells were treated with Polycyclic Aromatic Hydrocarbons (PAHs) and Persistent Organic Pollutants (POPs). HL-60 cells were treated with Volatile Organic Compounds (VOCs). Following comparative analysis, we detected some specific expression patterns in each of the chemical groups. We determined that the 7 chemicals utilized herein were ivided into 3 chemical groups on the basis of the following 16 genes : HHEX, HLA-G, C1QBP, RHEBL1, PMAIP1, PHIP, HK2, NOTCH1, PRF1, SGK, PLK3, BGLAP, LOC389844, GDF15, NRF1 and ABCC2. Subsequently, the Haz- Chem Human array as used to group the chemicals.