scholarly journals Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3316
Author(s):  
Taku Kaitsuka ◽  
Masayuki Matsushita ◽  
Nobuko Matsushita

The sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylase and ADP-ribosyl transferases plays key roles in aging, metabolism, stress response, and aging-related diseases. SIRT2 is a unique sirtuin that is expressed in the cytosol and is abundant in neuronal cells. Various microRNAs were recently reported to regulate SIRT2 expression via its 3′-untranslated region (UTR), and single nucleotide polymorphisms in the miRNA-binding sites of SIRT2 3′-UTR were identified in patients with neurodegenerative diseases. The present review highlights recent studies into SIRT2-mediated regulation of the stress response, posttranscriptional regulation of SIRT2 by microRNAs, and the implications of the SIRT2–miRNA axis in aging-related diseases.

Author(s):  
L. M. Bezrukavnikova ◽  
N. N. Anokhin ◽  
E. S. Tsidilkovskaya

The studied single-nucleotide polymorphisms EPHX1 (rs1051740), SAD2 (rs4880), MP9 (rs17576) in persons exposed to asbestos dust are associated with elevated levels of lipid peroxidation catabolites, which confirms their significance in the development of asbestos-related bronchopulmonary pathology.


2016 ◽  
Vol 24 (3) ◽  
pp. 213 ◽  
Author(s):  
E.M. Abdel-Kafy ◽  
S.F. Darwish ◽  
D. ElKhishin

The Myostatin (MSTN), or Growth and Differentiation Factor 8 (GDF8), gene has been implicated in the double muscling phenomenon, in which a series of mutations render the gene inactive and unable to properly regulate muscle fibre deposition. Single nucleotide polymorphisms (SNPs) in the MSTN gene have been correlated to production traits, making it a candidate target gene to enhance livestock and fowl productivity. This study aimed to assess any association of three SNPs in the rabbit MSTN gene (c.713T>A in exon 2, c.747+34C>T in intron 2, and c.*194A>G in 3’-untranslated region) and their combinations, with carcass, production and reproductive traits. The investigated traits included individual body weight, daily body weight gain, carcass traits and reproductive traits. The 3 SNPs were screened using PCR-restriction fragment length polymorphism (RFLP)-based analysis and the effects of the different SNP genotypes and their combinations were estimated in a rabbit population. Additionally, additive and dominance effects were estimated for significant traits. The results found no significant association between the c.713 T>A SNP and all the examined traits. Allele T at the c.747+34C>T SNP was only significantly associated (P<0.05) with increased body weight at 12 wk of age. However, for the SNP residing in the 3’ untranslated region (c.*194A>G), allele G was significantly associated (P<0.05) with increased body weight and high growth rate. Genotype GG at the c.*194A>G SNP also had positive effects on most carcass traits. The estimated additive genetic effect for the c.*194A>G SNP was significant (P<0.05) with most body weight, daily gain and carcass traits. No significant association was obtained between any MSTN SNPs and reproductive traits. In the combinations analysis, regardless of the genotypes of SNPs at c.713T>A and c.747+34C>T, GG at the c.*194A>G SNP correlated with highest values in body weight and daily weight gain. In conclusion, the ‘G’ allele at the c.*194A>G SNP had positive effects on growth and carcass traits and so could be used as a favourable allele in planning rabbit selection. Further population-wide studies are necessary to test the association of the c.*194A>G SNP with carcass traits. We also recommend evaluation of the potential effects of the c.*194A>G SNP on MSTN gene expression.


2005 ◽  
Vol 90 (2) ◽  
pp. 1123-1129 ◽  
Author(s):  
Hua Wang ◽  
Zhengxian Zhang ◽  
Winston Chu ◽  
Terri Hale ◽  
Judith J. Cooper ◽  
...  

IL-6 levels and polymorphisms have been implicated in type 2 diabetes mellitus (T2DM) and insulin resistance. The IL-6 receptor (IL-6R) comprises two subunits, IL-6R and gp130, of which IL-6R confers specificity to IL-6 action and is located in a region of replicated linkage to T2DM on chromosome 1q21. We screened this gene for variation in Northern European Caucasian and African-American ethnic groups. We identified 11 variants with a minor allele frequency over 5%, including two amino acid changes (D358A and V385I) and four variants in the 3′ untranslated region. No variant was associated with obesity or measures of insulin sensitivity, but two single nucleotide polymorphisms in the 3′ untranslated region showed a trend to an association with T2DM in all Caucasians, and three single nucleotide polymorphisms, including D358A, showed a trend (P < 0.06) to an association with T2DM among the subset of Northern European Caucasians. Variant V385I was unique to African-Americans and was significantly associated with diabetes and diabetic nephropathy (P < 0.05). Among individuals heterozygous for the four variants in the transcribed sequence, one allele was significantly overrepresented, thus suggesting the existence of a regulatory variant controlling mRNA stability or expression. IL-6R is not likely to explain the linkage to diabetes in this region, but our work supports a minor role of variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA levels and possibly levels of soluble IL-6R.


PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0156450 ◽  
Author(s):  
Albina N. Minlikeeva ◽  
Richard W. Browne ◽  
Heather M. Ochs-Balcom ◽  
Catalin Marian ◽  
Peter G. Shields ◽  
...  

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