Department Of Biochemistry And Microbial Sciences

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    Analysis of the Inhibitory Effect of hsa-miR-145-5p and hsa-miR-203a-5p on Imatinib-Resistant K562 Cells by GC/MS Metabolomics Method
    (American Chemical Society, 2023-09-14T00:00:00) Singh, Priyanka; Yadav, Radheshyam; Verma, Malkhey; Chhabra, Ravindresh
    Imatinib (IM) resistance is considered to be a significant challenge in the management of chronic myeloid leukemia (CML). Previous studies have reported that hsa-miR-145-5p and hsa-miR-203a-5p can overcome IM resistance and hsa-miR-203a-5p can alter glutathione metabolism in IM-resistant cells. The purpose of this study was to examine whether hsa-miR-145-5p or hsa-miR-203a-5p counters IM resistance by targeting the overall metabolic profile of IM-resistant K562 cells. The metablic profiling of cell lysates obtained from IM-sensitive, IM-resistant, and miR-transfected IM-resistant K562 cells was carried out using the GC-MS technique. Overall, 75 major metabolites were detected, of which 32 were present in all samples. The pathway analysis of MetaboAnalyst 5.0 revealed that the majorly enriched pathways included glucose metabolism, fatty acid biosynthesis, lipogenesis, and nucleotide metabolism. Eleven of identified metabolites, l-glutamine, l-glutamic acid, l-lactic acid, phosphoric acid, 9,12-octadecadienoic acid, 9-octadecenoic acid, myristic acid, palmitic acid, cholesterol, and ?-alanine, appeared in enriched pathways. IM-resistant cells had comparatively higher concentrations of all of these metabolites. Notably, the introduction of hsa-miR-145-5p or hsa-miR-203a-5p into resistant cells resulted in a decrease in levels of these metabolites. The efficacy of miR-203a-5p was particularly remarkable in comparison with miR-145-5p, as evidenced by partial least-squares-discriminant analysis (PLS-DA), which showed a high level of similarity in metabolic profile between IM-sensitive K562 cells and IM-resistant cells transfected with hsa-miR-203a-5p. The results indicate that GC-MS-based metabolic profiling has the potential to distinguish between drug-resistant and -sensitive cells. This approach can also be used to routinely monitor therapeutic response in drug-resistant patients, thus, enabling personalized therapy. � 2023 American Society for Mass Spectrometry. Published by American Chemical Society. All rights reserved.
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    Comparative metabolic profiling of vetiver (Chrysopogon zizanioides) and maize (Zea mays) under lead stress
    (Elsevier Ltd, 2018) Pidatala, V.R.; Li, K.; Sarkar, D.; Wusirika, R.; Datta, R.
    Lead (Pb) contamination of residential soils in United States is attributed to use of Pb based paints prior to 1978 and their deterioration and accumulation in surface soils. Exposure to Pb due to ingestion and inhalation of Pb laden soil and dust causes neurological disorders, renal disorders, developmental and behavioral problems, particularly in children under the age of six. Vetiver grass is one of the leading choices for Pb remediation due to its ability to hyperaccumulate Pb, in addition to high biomass. In order to understand the effect of Pb on vetiver metabolic pathways, we compared the global metabolic changes in vetiver with that of maize, a Pb susceptible plant under Pb stress. Vetiver showed massive increase in levels of key metabolites in response to Pb, including amino acids, organic acids and coenzymes. Maize showed very modest increase in some of the same metabolites, and no change in others. The results provide the first indication of the difference in metabolic response of the hyperaccumulator, vetiver to lead stress as compared to maize. ? 2017 Elsevier Ltd