Unknown,Transcriptomics,Genomics,Proteomics

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Lipoic acid prevents Cr6+ induced cell transformation and the associated genomic dysregulation.

ABSTRACT: Investigation of the transcription profile of cells transformed by Cr6+ in vivo was undertaken. The objective was to elucidate genomic changes underlying the mechanism of action of the carcinogenic dose of Cr6+and their prevention using metabolic antioxidant Lipoic acid (LA). Cr6+ was administered intraperitoneally to LPS+TPA challenged Swiss albino mice in host mediated cell transformation assay using peritoneal macrophages in vivo. The cell transforming potential of Cr6+ test doses was validated by gain of anchorage independent growth potential in soft agar and loss of Fc receptor on target cells. LA was administered in equimolar doses. Compared to non-transformed cells, the gene expression profile of transformed cells was found to be dysregulated substantially and in dose dependent manner. Genes showing down regulation were found to be involved in tumour suppression; apoptosis, DNA repair, and cell-cycle. A similar response was noted in the genes pertaining to immune system, morphogenesis, cell-communication, energy-metabolism, and biosynthesis. The co-administration of lipoic acid prevented the transcription dysregulation and cell transformation by Cr6+ in vivo. The influenced pathways seem to be crucial for progression as well as mitigation of Cr toxicity; and their response to LA indicated their critical role in mechanism of anti-carcinogenic action of LA. Results are of importance to mitigate Cr6+ induced occupational cancer hazard. Agilent one-color experiment, Organism: Mus musculus, Agilent-Whole Genome Mouse 4x44k (AMADID: 14868), Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)

ORGANISM(S): Mus musculus

SUBMITTER: Dr Sushil Kumar

PROVIDER: E-GEOD-41419 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Lipoic acid prevents Cr(6+) induced cell transformation and the associated genomic dysregulation.

Kumar Sushil S Nigam Akanksha A Priya Shivam S Bajpai Preeti P Budhwar Roli R

Environmental toxicology and pharmacology 20130314 1

Investigation of the transcription profile of cells transformed by Cr(6+) in vivo was undertaken. The objective was to elucidate genomic changes underlying the mechanism of action of the carcinogenic dose of Cr(6+)and their prevention using metabolic antioxidant lipoic acid (LA). Cr(6+) was administered intraperitoneally to LPS+TPA challenged Swiss albino mice in host mediated cell transformation assay using peritoneal macrophages in vivo. The cell transforming potential of Cr(6+) test doses was ...[more]

PMID: 23608068

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Project description:Ethnopharmacological relevance: Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine formula derived from Yupingfensan, an ancient formula widely used to treat respiratory diseases such as repeated respiratory infection, allergic rhinitis, bronchitis, and asthma. In recent years, GBFXD has been applied to efficaciously and safely treat asthma. However, the mechanism of GBFXD is still not fully elucidated. Aim of the study: A label-free proteomic method was to employed to explore the protective mechanism of GBFXD in respiratory syncytial virus (RSV)-ovalbumin (OVA)-induced chronic persistent asthmatic mice. Materials and methods: After RSV-OVA challenge, mice were orally administered GBFXD at a dose of 36 g/kg/d accompanied with OVA nasal spray once every 3 days for 28 days. The label-free proteomics-based liquid chromatography-tandem mass spectrometry method was used to explore the differentially abundant proteins (DAPs) in the serum from model mice compared with that in control mice (M:C), and in GBFXD-treated mice compared with that in model mice (G:M). We utilized OmicsBean (http://www.omicsbean.cn), a multi-omics data analysis platform, to perform bioinformatics analysis of DAPs. Enzyme-linked immunosorbent assay and Western Blotting were performed to measure the levels of related proteins and verify the results of proteomics analysis. Results: A total of 69 significant DAPs were identified including 39 in M:C, 46 in G:M, and 16 common differential proteins. Bioinformatics analysis revealed that the DAPs of M:C were mainly involved in inflammatory response and were related to lipid metabolism. However, the DAPs of G:M mostly participated in stress response, inflammatory response, and epithelial cell proliferation. Serum levels of Apoa-1, Apoc-1, Cfd, and Lrg1, EGFR and Lrg1 in the lungs were consistent with the results of proteomic analysis. Apoa-1 and Apoc-1 are closely related to cholesterol transport, lipid metabolism balance, and airway epithelial integrity; Cfd participates in immune response, affecting the occurrence and development of inflammation; EGFR and Lrg1 are involved in epithelial cell proliferation, influencing the process of airway remodeling. Conclusions: GBFXD may affect inflammatory and immune responses of asthma by regulating cholesterol transport and complement factor activation. Furthermore, it could repair damaged airway epithelium and avoid airway remodeling to prevent and treat asthma.

Dataset Information

Lipoic acid prevents Cr6+ induced cell transformation and the associated genomic dysregulation.

Publications

Lipoic acid prevents Cr(6+) induced cell transformation and the associated genomic dysregulation.

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