Department Of Human Genetics And Molecular Medicine

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Author: search.filters.author.Singh, SandeepSubject: search.filters.subject.Gene Expression

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    Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment
    (2012) Singh, Sandeep; Raina, Varsheish; Chavali, Pavithra Lakshminarsimhan; Dubash, Taronish; Kadreppa, Sreenath; Parab, Pradeep; Chattopadhyay, Samit
    Background: GAD65 (Glutamic acid decarboxylase 65 KDa isoform) is one of the most important auto-antigens involved in Type 1 diabetes induction. Although it serves as one of the first injury markers of ?-islets, the mechanisms governing GAD65 expression remain poorly understood. Since the regulation of GAD65 is crucial for the proper functioning of insulin secreting cells, we investigated the stress induced regulation of GAD65 transcription.Results: The present study shows that SMAR1 regulates GAD65 expression at the transcription level. Using a novel protein-DNA pull-down assay, we show that SMAR1 binding is very specific to GAD65 promoter but not to the other isoform, GAD67. We show that Streptozotocin (STZ) mediated DNA damage leads to upregulation of SMAR1 and p53 expression, resulting in elevated levels of GAD65, in both cell lines as well as mouse ?-islets. SMAR1 and p53 act synergistically to up-regulate GAD65 expression upon STZ treatment.Conclusion: We propose a novel mechanism of GAD65 regulation by synergistic activities of SMAR1 and p53. ? 2012 Singh et al.; licensee BioMed Central Ltd.
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    miR-30c and miR-181a synergistically modulate p53?p21 pathway in diabetes induced cardiac hypertrophy
    (Springer New York LLC, 2016) Raut, Satish K.; Singh, Gurinder B.; Rastogi, Bhawna; Saikia, Uma Nahar; Mittal, Anupam; Dogra, Nilambra; Singh, Sandeep; Prasad, Rishikesh; Khullar, Madhu
    p53?p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53?p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53?p21 pathway in DbCM. ? 2016, Springer Science+Business Media New York.