The Role of miR-29/33 in Mitochondrial Hydroxymethylation Disturbance and Mitochondrial Dysfunction Induced by mtDNA Damage View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2013-2016

FUNDING AMOUNT

700000 CNY

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a complex metablic disease and associated with insulin resistance and mitochondrial dysfunction. Our results have investigated that the common mutations of mitochondrial DNA (mtDNA) are G3316A and T3394C in T2DM patients, and the specific mutations include both T3593C and A4833G in one case. Moreover, we also confirmed that elevated plasma levels of total free fatty acids (FFA) and saturated fatty acids with decrease of mtDNA, which is related to HOMA-IR. Recent studies imply that lower mtDNA content is related to DNA methylation disorders; FFA metabolism, mtDNA methylation and insulin signaling are regulated by miR-29a/b and miR-33a/b. We suppose that microRNAs (such as miR-29a/b and -33a/b) as key regulators involve in the DNA methylation disorder and mitochondrial dysfunction in T2DM with mtDNA damages. To verify the hypothesis, we will analyze the levels of 5-methylcytosine and 5-hydroxylmethycytosine of mtDNA in the models of differently expressed miR-29a/b and -33a/b after treatment with different concentrations of glucose, fatty acids and insulin. These results will demonstrate that whether these mutations play a role in the pathogenesis of T2DM, and the effects of miR-29a/b and -33a/b expression on mitochondrial dysfunction and disorder of 5-Hydroxymethylcytosine in Typ More... »

URL

http://npd.nsfc.gov.cn/projectDetail.action?pid=81271919

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