Increased Oxidative Damage of RNA in Early-Stage Nephropathy in db/db Mice

To evaluate RNA oxidation in the early stage of diabetic nephropathy, we applied an accurate method based on isotope dilution high-performance liquid chromatography-triple quadruple mass spectrometry to analyze the oxidatively generated guanine nucleosides in renal tissue and urine from db/db mice of different ages. We further investigated the relationship between these oxidative stress markers, microalbumin excretion, and histological changes. We found that the levels of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) were increased in the urine and renal tissue of db/db mice and db/db mice with early symptoms of diabetic nephropathy suffered from more extensive oxidative damage than lean littermate control db/m mice. Importantly, in contrast to the findings in db/m mice, the 8-oxoGuo levels in the urine and renal tissue of db/db mice were higher than those of 8-oxodGuo at four weeks. These results indicate that RNA oxidation is more apparent than DNA oxidation in the early stage of diabetic nephropathy. RNA oxidation may provide new insight into the pathogenesis of diabetic nephropathy, and urinary 8-oxoGuo may represent a novel, noninvasive, and easily detected biomarker of diabetic kidney diseases if further study could clarify its source and confirm these results in a large population study

Distributions of the 20 most common HLA five-locus haplotypes in the seven geographic regions of China.

<p>(A) China; (B) Northeast China (NE); (C) North China (NC); (D) Northwest China (NW); (E) East China (EC); (F) Central China (CC); (G) South China (SC); (H) Southwest China (SW).</p

Numbers of HLA alleles observed in 169,995 Chinese individuals.

<p>^a: data from <a href="http://www.ebi.ac.uk/ipd/imgt/hla/stats.html" target="_blank">http://www.ebi.ac.uk/ipd/imgt/hla/stats.html</a>, 3.16 Release, April, 2014.</p><p>Numbers of HLA alleles observed in 169,995 Chinese individuals.</p

Distinctive HLA five-locus haplotypes in Southwest China and South China.

<p>Distinctive HLA five-locus haplotypes in Southwest China and South China.</p

Geographic regions of China. Northeast China (NE), North China (NC), Northwest China (NW), East China (EC), Central China (CC), South China (SC), and Southwest China (SW).

<p>Note: Taiwan, Hong Kong and Macau were not included in this study.</p

Numbers of HLA alleles according to several categories observed in the seven geographic regions.

<p>CWD: common and well-documented allele; Rare: rare allele;</p><p>Not observed: alleles that were absent in one region;</p><p>Shared in all regions: alleles that were observed in all regions;</p><p>Unique in one region: alleles that were only observed in one region.</p><p>Numbers of HLA alleles according to several categories observed in the seven geographic regions.</p

HLA Matching within and between populations from each of the seven regions of China (matching rates).

<p>The matching rates within and between regions were plotted as a matrix. Each data point represented the matching rate between two particular regions with names in the corresponding columns and rows. The matching rates were grouped in three categories. The high-level matching rates (> 0.00003) were indicated in <b>bold type</b>. The medium-level matching rates (0.00002–0.00003) and the low-level matching rates (< 0.00002) were indicated in <i>italic type</i> and normal type respectively.</p><p>HLA Matching within and between populations from each of the seven regions of China (matching rates).</p

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present