Irreversible Inflammation is Associated with Decreased Levels of the α1-, β1-, and α2-Subunits of sGC in Human Odontoblasts

Irreversible Inflammation is Associated with Decreased Levels of the α1-, β1-, and α2-Subunits of sGC in Human Odontoblasts
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DOI:
10.1177/0022034510390808
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发表时间:
2011-04-01
影响因子:
7.6
通讯作者:
Raab, W. H. -M.
Raab, W. H. -M.
中科院分区:
医学1区
文献类型:
--
作者:
Korkmaz, Y.;Lang, H.;Raab, W. H. -M.

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一氧化氮(NO)受体酶可溶性鸟苷酸环化酶(sGC)含有一个作为α β异二聚体的血红素辅基,两种异二聚体亚型(α(1)β(1),α(2)β(1))被表征为具有酶活性。为了测试成牙本质细胞中sGC的不可逆炎症依赖性调节,我们将健康和发炎的人类第三磨牙的脱钙冷冻切片与针对β-肌动蛋白、硝基酪氨酸、诱导型一氧化氮合酶(iNOS)、sGC的α(1)-、β(1)-和α(2)-亚基的抗体孵育,并通过定量免疫组织化学在蛋白质水平上对其进行分析。不可逆炎症诱导成牙本质细胞中硝基酪氨酸和iNOS的信号强度增加,sGC的α(1)-、β(1)-和α(2)-亚基减少。炎症介质、活性氧和氮类物质可能会损害成牙本质细胞中α 1、β 1和α 2亚基的表达。sGC在炎症成牙本质细胞中蛋白水平的降低与sGC介导NO在健康中的生物学效应的关键作用是一致的。
The nitric oxide (NO) receptor enzyme soluble guanylate cyclase (sGC) contains one prosthetic heme group as an alpha beta heterodimer, and two heterodimer isoforms (alpha(1)beta(1), alpha(2)beta(1)) were characterized to have enzyme activity. To test the irreversible inflammation-dependent regulation of sGC in odontoblasts, we incubated decalcified frozen sections of healthy and inflamed human third molars with antibodies against beta-actin, nitrotyrosine, inducible nitric oxide synthase (iNOS), alpha(1)-, beta(1)-, and alpha(2)-subunits of sGC and analyzed them at protein levels by quantitative immunohistochemistry. The irreversible inflammation induced an increase in the signal intensities for nitrotyrosine and iNOS and a decrease for the alpha(1)-, beta(1)-, and alpha(2)-subunits of sGC in odontoblasts. Inflammatory mediators, reactive oxygen, and nitrogen species may impair the expression of the alpha(1)-, beta(1)-, and alpha(2)-subunits in odontoblasts. The decrease of sGC at the protein level in inflamed odontoblasts is compatible with a critical role for sGC to mediate biological effects of NO in health.