Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice.
Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice.
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DOI：
10.1371/journal.pone.0100912
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Piantadosi CA
中科院分区：
文献类型：
--
作者：
Bartz RR;Fu P;Suliman HB;Crowley SD;MacGarvey NC;Welty-Wolf K;Piantadosi CA
急性肾损伤（阿基）导致脓毒症多系统器官衰竭的高发病率和死亡率。然而，脓毒症诱导的阿基后肾功能的恢复表明能量产生途径的主动修复。在这里，我们在小鼠中测试了金黄色葡萄球菌败血症损伤肾脏线粒体DNA（mtDNA）并激活mtDNA修复和线粒体生物合成的假设。在野生型C57 Bl/6 J和考克斯-8 GFP标记的骨髓报告小鼠中，通过用S.金黄色。在感染后0小时（对照）、24小时或48小时收获存活小鼠的肾脏，并评价肾脏炎症、氧化应激标志物、mtDNA含量和线粒体生物发生标志物以及OGG 1和UDG线粒体DNA修复酶。我们检查了线粒体报告小鼠的肾脏染色密度和分布的变化。S.金黄色葡萄球菌脓毒症诱导肾脏TNF、IL-10和Ngal mRNA急剧扩增，肾脏mtDNA含量降低，肾小管和肾小球细胞死亡增加，蛋白质羰基和8-OHdG积累增加。随后，线粒体DNA修复和线粒体生物合成的证据是OGG 1水平升高和NRF-1，NRF-2和mtTFA表达的显着增加。总体而言，肾线粒体质量，柠檬酸合酶mRNA和蛋白质跟踪，增加与线粒体GFP荧光的变化平行，特别是在近端肾小管在肾皮质和髓质。亚致死性S.因此，金黄色葡萄球菌脓毒症诱导广泛的肾线粒体损伤，其触发肾mtDNA修复蛋白OGG 1和线粒体生物合成的诱导，作为全身性细菌感染后的显著消退机制。
Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection.
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影响因子：
19.6
作者：
AGARWAL, A;BALLA, J;NATH, KA
通讯作者：
NATH, KA
DOI：
10.1016/j.bbrc.2007.10.123
发表时间：
2007-12-28
影响因子：
3.1
作者：
Jaloszynski, Pawel;Murata, Soichiro;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki
影响因子：
19.6
作者：
Chertow, G. M.;Soroko, S. H.;Mehta, R. L.
通讯作者：
Mehta, R. L.
DOI：
10.1164/rccm.201106-1152oc
发表时间：
2012-04-15
影响因子：
24.7
作者：
MacGarvey, Nancy Chou;Suliman, Hagir B.;Piantadosi, Claude A.
通讯作者：
Piantadosi, Claude A.
DOI：
10.1152/ajplung.00210.2011
发表时间：
2011-12-01
影响因子：
4.9
作者：
Chouteau, Joshua M.;Obiako, Boniface;Gillespie, Mark N.
通讯作者：
Gillespie, Mark N.