Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc
Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc
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DOI：
10.1002/jor.1100170607
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发表时间：
1999-11-01
影响因子：
2.8
通讯作者：
Urban, JPG
中科院分区：
文献类型：
--
作者：
Ishihara, H;Urban, JPG
椎间盘是人体内最大的无血管结构;因此，O-2浓度存在陡峭的梯度，在椎间盘中心，Po-2下降到低至1% O-2。我们研究了O-2浓度对O-2消耗率，乳酸生产，硫酸盐和脯氨酸掺入牛尾盘的影响。我们还研究了能量产生途径的代谢抑制剂对示踪剂掺入的影响。将来自外环和髓核的样品在1- 21%O-2中孵育24小时。在孵育的最后4小时期间测量速率。当O-2浓度从10%降低到1%时。O-2消耗率下降了约75%，乳酸生产率几乎翻了一番;因此，牛椎间盘显示出积极的进行性巴斯德效应。[H-3]脯氨酸和[S-35]硫酸盐的掺入率在1%O-2时最低。在细胞核中，[S-35]掺入率在5%O-2时达到峰值，比21%O-2时高30%，比1%O-2时高150%。竞争性糖酵解抑制剂2-脱氧葡萄糖，氧化磷酸化解偶联剂2，4-二硝基苯酚和氧化磷酸化抑制剂叠氮化钠均显著降低硫酸盐掺入。这些结果，加上先前的测量CO2的生产率，表明功能上显着的一部分光盘的能量是由氧化磷酸化。然而，据报道，低水平的Po-2 2，4-二硝基苯酚和叠氮化钠可减少关节软骨中的硫酸盐掺入，关节软骨是一种几乎完全从糖酵解获得能量的组织。
The intervertebral disc is the largest asvacular structure in the body; consequently, there are steep gradients in O-2 concentration, with Po-2 falling to as low as 1% O-2 in the centre of the disc. We investigated the effect of O-2 concentration on the rates of O-2 consumption, lactate production, and sulphate and proline incorporation in bovine caudal discs. We also investigated the effects of metabolic inhibitors of energy production pathways on tracer incorporation. Samples from the outer annulus and nucleus pulposus were incubated for 24 hours in 1-21% O-2 Rates were measured during the last 4 hours of incubation. As O-2 concentration was reduced from 10 to 1% O-2. O-2 consumption rates fell by around 75% and lactate production rates almost doubled; the bovine discs thus showed a positive progressive Pasteur effect. Incorporation rates of [H-3]proline and [S-35]sulphate were lowest at 1% O-2 In the nucleus, but not in the outer annulus, the rate of [S-35]incorporation peaked at 5% O-2, where it was 30% greater than at 21% O-2 and 150% greater than at 1% O-2 The competitive glycolysis inhibitor 2-deoxyglucose, the oxidative phosphorylation uncoupler 2,4-dinitrophenol, and the oxidative phosphorylation inhibitor sodium azide all markedly reduced sulphate incorporation. These results, together with previous measurements of CO2 production rates, suggest that a functionally significant fraction of the disc's energy is supplied by oxidative phosphorylation. However, low levels of Po-2 2,4-dinitrophenol, and sodium azide have been reported to reduce sulphate incorporation in articular cartilage, a tissue that derives its energy almost entirely from glycolysis.