Polybacterial Periodontal Pathogens Alter Vascular and Gut BH4/nNOS/NRF2-Phase II Enzyme Expression.
Polybacterial Periodontal Pathogens Alter Vascular and Gut BH4/nNOS/NRF2-Phase II Enzyme Expression.
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多分裂牙周病原体改变了血管和肠道BH4/NNOS/NRF2-相II酶表达。
DOI：
10.1371/journal.pone.0129885
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kesavalu L
中科院分区：
文献类型：
--
作者：
Gangula P;Ravella K;Chukkapalli S;Rivera M;Srinivasan S;Hale A;Channon K;Southerland J;Kesavalu L
牙周病是一种高度流行的慢性炎症性疾病，与龈下腔复杂的微生物感染有关。最近，美国心脏协会支持牙周病和动脉粥样硬化性血管疾病之间存在世纪的联系。我们最近发现，多菌性牙周感染导致主动脉粥样硬化和血脂谱的调节，但其潜在机制尚未得到证实。一氧化氮（NO）合成和四氢生物蝶呤（BH 4），一氧化氮合酶（NOS）的辅因子的改变长期以来已被证明与血管功能障碍和胃肠动力障碍有关。我们试图研究牙周感染导致血管和胃肠道平滑肌松弛改变的机制，重点是BH 4/nNOS途径。此外，我们还研究了口腔感染如何改变血管和GI标本中的抗氧化系统（NRF 2-II相酶表达）。将8周龄的雄性ApoEnull小鼠假感染或用主要牙周细菌牙龈卟啉单胞菌（Porphyromonas gingivalis）、齿垢密螺旋体（Treponema denticola）和坦纳氏菌（Tannerella dentithia）的混合物经口感染16周以诱导实验性牙周炎。在牙周病原体感染结束时收集血清、血管（肠系膜）、胃和结肠标本。与假感染对照相比，细菌感染诱导BH 4水平、BH 4：BH 2 +B比率以及一氧化氮水平显著降低（p<0.05）。此外，我们确定了在肠系膜动脉和结肠组织中，与对照相比，感染小鼠中eNOS二聚化、nNOS二聚化和BH 4生物合成酶; GCH-1、DHFR和NRF 2 & II相酶的蛋白表达显著（p<0.05）降低。然而，我们没有发现nNOS/BH 4蛋白在感染和假感染小鼠胃组织中的表达差异。这表明多细菌感染可引起血管和结肠BH 4/nNOS/NRF 2途径的显著变化，这可能导致血管松弛和结肠运动受损。
Periodontal disease is a highly prevalent chronic inflammatory disease and is associated with complex microbial infection in the subgingival cavity. Recently, American Heart Association supported a century old association between periodontal disease and atherosclerotic vascular disease. We have recently shown that polybacterial periodontal infection led to aortic atherosclerosis and modulation of lipid profiles; however the underlying mechanism(s) has not been yet demonstrated. Altered nitric oxide (NO) synthesis and tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthases (NOS) has long been shown to be associated with vascular dysfunction and gastrointestinal motility disorders. We sought to examine the mechanism of periodontal infection leading to altered vascular and gastrointestinal smooth muscle relaxation, focusing on the BH4/nNOS pathways. In addition, we also have investigated how the antioxidant system (NRF2-Phase II enzyme expression) in vascular and GI specimens is altered by oral infection. Eight week old male ApoEnull mice were either sham-infected or infected orally for 16 weeks with a mixture of major periodontal bacteria Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia to induce experimental periodontitis. Serum, vascular (mesenteric), stomach, and colon specimens were collected at the end of periodontal pathogen infection. Bacterial infection induced significant (p<0.05) reductions in the levels of BH4,in ratio of BH4:BH2+B and also in nitric oxide levels compared to sham-infected controls. In addition, we identified a significant (p<0.05) reduction in eNOS dimerization, nNOS dimerization and protein expression of BH4 biosynthesis enzymes; GCH-1, DHFR and NRF2 & Phase II enzymes in infected mice versus controls in both mesenteric artery and colon tissues. However, we found no differences in nNOS/BH4 protein expression in stomach tissues of infected and sham-infected mice. This suggests that a polybacterial infection can cause significant changes in the vascular and colonic BH4/nNOS/NRF2 pathways which might lead to impaired vascular relaxation and colonic motility.
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影响因子：
3.5
作者：
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通讯作者：
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