Cytokine-mediated bone resorption is cytochrome P-450 dependent. Student Research Award 1998.
Cytokine-mediated bone resorption is cytochrome P-450 dependent. Student Research Award 1998.
复制标题
细胞因子介导的骨吸收依赖于细胞色素 P-450。
DOI：
10.1053/hn.1999.v121.a101034
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Chole,R
中科院分区：
文献类型：
--
作者：
Young,N;Chole,R
局部骨质流失导致慢性中耳炎的发病率。虽然骨重建的细胞事件已经被很好地建立，但它们的调节仍然知之甚少。各种细胞因子，包括肿瘤坏死因子-α、白细胞介素-1 β和干扰素-γ，单独使用和联合使用，是骨吸收的强有力诱导剂。一氧化氮（NO）是一氧化氮合酶（NOS）作用于L-精氨酸形成NO的产物。细胞色素P-450是一种在结构和功能上与NOS相似的酶，也可能在各种细胞系统中的NO产生中起作用。本研究的目的是阐明细胞色素P-450在骨中的可能作用。在这项研究中，用西咪替丁和克霉唑（细胞色素P-450 IIIA家族的选择性抑制剂）和7-乙氧基试卤灵（细胞色素P-450的非特异性抑制剂）阻断了苦参碱诱导的骨吸收。还观察到NO的伴随减少。这种效应可能是由于细胞色素P-450是骨中NOS的首选替代途径或提供了一种必需的辅助因子。
Localized bone loss leads to much of the morbidity of chronic otitis media. Although the cellular events of bone remodeling have been well established, their regulation remains Poorly understood. Various cytokines, including tumor necrosis factor-α, interleukin-1β, and interferon-γ, used alone and in combination, are Powerful inducers of bone resorption. One of the modulators of cytokine-induced bone resorption is nitric oxide (NO), a product of the action of NO synthase (NOS) on L-arginine to form NO. Cytochrome P-450, an enzyme that is similar to NOS both structurally and functionally, may also have a role in NO production in various cellular systems. The goal of this study was to elucidate a Possible role of cytochrome P-450 in bone. In this study cytokine-induced bone resorption was blocked with cimetidine and clotrimazole, which are selective inhibitors of the cytochrome P-450 IIIA family and 7-ethoxyresorufin, a nonspecific cytochrome P-450 inhibitor. A concomitant reduction of NO was also observed. This effect may be explained by cytochrome P-450 being a preferred alternative pathway or providing an essential cofactor to NOS in bone.